RESUMO
OBJECTIVE: To assess the role of antiseizure medication (ASM) regimens and other factors in relation to the occurrence of intrauterine foetal death (IUFD) in pregnant women with epilepsy (WWE) enrolled in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (APR). RESULTS: IUFDs occurred in 70 (3.01 %) of 2,323 prospective pregnancies from WWE with known outcomes in the APR. Factors associated with IUFD occurrence included older maternal age, enrolment in the APR at an earlier stage of pregnancy, history of pregnancies which did not result in livebirths, parental history of foetal malformations, and maternal use of carbamazepine, lamotrigine or ethosuximide. Individual ASM dosages were not associated with IUFD occurrence. Relative to no exposure, the risk of IUFD increased with the increasing number of ASMs used in combination (2 ASMs: relative risk, RR = 5.45 [95 % CI: 0.73-41.80]; 3 ASMs: RR = 10.70 [95 % CI: 1.27-90.17]), >3 ASMs: RR = 10.70 [95 % CI: 1.27-90.17]), but this finding was attenuated after adjusting for other factors implicated in IUFD occurrence. Several ASM pairs were associated with an increased risk of IUFD relative to no exposure, but these associations were lost after accounting for confounders. CONCLUSIONS: Although it is possible that prenatal ASM exposure may increase the risk of IUFD, other non-pharmacological factors are more relevant to the occurrence to IUFD in pregnant WWE.
Assuntos
Epilepsia , Morte Fetal , Gravidez , Feminino , Humanos , Estudos Prospectivos , Austrália/epidemiologia , Morte Fetal/etiologia , Natimorto/epidemiologia , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/induzido quimicamenteRESUMO
OBJECTIVES: To trace (i) changes in Australian Pregnancy Register (APR) records concerning antiseizure medications (ASMs) prescribed for women with epilepsy (WWE) over the course of 24 years and correlate the changes with (ii) rates of occurrence of pregnancies involving foetal malformations, (iii) the body organs involved in the malformations, and (iv) freedom from epileptic seizures. RESULTS: Use of valproate and carbamazepine decreased progressively, use of lamotrigine remained relatively static, and the use of levetiracetam increased progressively, whereas the use of topiramate first increased and then fell again, associated with a temporary increase in malformation-associated pregnancy rate. More serious malformations, such as spina bifida, became less frequent, whereas more trivial ones tended to increase, whereas epileptic seizure freedom rates improved. CONCLUSIONS: The increasing use of newer ASMs in pregnant women has been associated with overall advantages in relation to the frequency and severity of foetal malformation and with advantages in relation to freedom from epileptic seizures.
Assuntos
Epilepsia , Complicações na Gravidez , Feminino , Gravidez , Humanos , Austrália/epidemiologia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Anticonvulsivantes/efeitos adversos , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Lamotrigina/uso terapêutico , Ácido Valproico/uso terapêutico , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologiaRESUMO
OBJECTIVE: To investigate in the Australian Pregnancy Register of Antiepileptic Drugs patterns of fetal malformation associated with intrauterine exposure to particular currently available antiseizure medications taken by women with epilepsy. RESULTS: There was statistically significant evidence (P < 0.05) of an increased hazard of fetal malformation associated with exposure to valproate, carbamazepine, topiramate, zonisamide, and with conception after assisted fertilization, but a reduced hazard in the offspring of women who continued to smoke during pregnancy. Valproate exposure was associated with malformations in a wide range of organs and organ systems, carbamazepine and topiramate with hydronephrosis, topiramate also with hypospadias, zonisamide with spina bifida and assisted fertilization with heart and great vessel maldevelopment. CONCLUSIONS: Prenatal valproate exposure appears to interfere with the development of many if not all, fetal tissues. It seems likely that prenatal exposure to carbamazepine and topiramate, and possibly exposure to zonisamide, but also some process related to in vitro fertilization, may more selectively affect the normal development of particular fetal tissues or organs.
Assuntos
Anormalidades Induzidas por Medicamentos , Complicações na Gravidez , Gravidez , Masculino , Feminino , Humanos , Ácido Valproico/uso terapêutico , Topiramato/uso terapêutico , Zonisamida/uso terapêutico , Austrália , Anticonvulsivantes/efeitos adversos , Carbamazepina/uso terapêutico , Complicações na Gravidez/tratamento farmacológicoRESUMO
OBJECTIVES: To investigate control of epileptic seizures during pairs of successive pregnancies in antiseizure medication (ASM)-treated women with epilepsy. MATERIALS AND METHODS: Analysis of seizure freedom rates during 436 pairs of successive pregnancies in Australian women with epilepsy, in nearly all instances long-standing epilepsy. RESULT: There was a higher rate of seizure-free second pregnancies compared with first paired pregnancies (63.1% vs. 51.4%; Relative Risk (R.R.) = 1.2277; 95% CI 1.0930, 1.3789) and of seizure-free pre-pregnancy years before second as compared with first paired pregnancies in the same women (63.6% vs. 52.4%; R.R. = 1.2616; 95% CI 1.1337, 1.4040). In 108 women whose ASM therapy was unaltered throughout both of their pregnancies, the seizure-freedom rate was higher in the second of the paired pregnancies (82.4% vs. 69.4%; R.R. = 1.1867, 95% CI 1.0189, 1.3821). CONCLUSIONS: Altered ASM therapy after the first of a pair of successive pregnancies did not fully account for the better overall seizure control in the corresponding second pregnancies. Some additional factor may have been in operation, possibly a greater preparedness to undertake a further pregnancy if seizures were already fully controlled.
Assuntos
Epilepsia , Complicações na Gravidez , Anticonvulsivantes/uso terapêutico , Austrália/epidemiologia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Convulsões/tratamento farmacológico , Convulsões/epidemiologiaRESUMO
OBJECTIVES: To study factors that affected previous epileptic seizure control throughout pregnancy, during labour, and in the post-natal weeks. MATERIALS & METHODS: Analysis of data concerning seizure freedom that was available at various stages of 2337 pregnancies in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs, mainly employing multiple variable logistic regression techniques. RESULTS: Based on data available at the outset of pregnancy, the risk of seizure-affected that is, not seizure-free pregnancy was statistically significantly (p < .05) higher in pregnancies where there was previously uncontrolled epilepsy (78.1% vs. 20.8%) and focal epilepsy (51.3% vs. 39.7%), and decreased with later onset-age epilepsy (41.8% vs. 52.2% with onset before age 13 years), The risk did not differ between initially antiseizure medication (ASM)-treated or untreated pregnancies. For epilepsy receiving ASM therapy, 90.6% of 160 pregnancies of women with uncontrolled focal epilepsy that began before the age of 13 were seizure-affected. None of the above factors influenced the risk of seizures during labour, though having seizures during pregnancy increased the hazard (3.93 vs. 0.6%). Either ASM-treated pregnancy or labour being seizure-affected increased the risk of post-partum period seizures (33.0% vs. 6.67% for both stages being seizure-free). Use of particular ASMs had no statistically significant effect on the seizure control situation at any of the pregnancy stages studied. CONCLUSIONS: Obtaining full seizure control before pregnancy appeared to be the main factor in maintaining seizure freedom during pregnancy, labour and the post-natal weeks.
Assuntos
Epilepsias Parciais , Epilepsia , Complicações na Gravidez , Adolescente , Anticonvulsivantes/uso terapêutico , Austrália/epidemiologia , Epilepsias Parciais/tratamento farmacológico , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Convulsões/tratamento farmacológico , Convulsões/epidemiologiaRESUMO
OBJECTIVES: To utilize data from the Australian Register of Antiepileptic Drugs in Pregnancy (APR) to determine the hazard of fetal malformation in the subsequent pregnancy or pregnancies in women with epilepsy following a pregnancy associated with a fetal malformation, and to identify factors relevant to the hazard. RESULTS: There was a 7.4% initial pregnancy fetal malformation rate. The subsequent pregnancy malformation rate was 4.2% if there was no initial pregnancy malformation, but 21.2% if there was an initial pregnancy malformation (O.R. = 6.1448, 95% C.I. 2.3396, 16.1386). For pregnancies where antiseizure medication (ASM) therapy was unchanged between pregnancies (N = 196), the initial pregnancy malformation rate was 10.2%, but 30.0% in the subsequent pregnancy if there was a malformation in the initial pregnancy, and 2.35% if there was none (O.R. = 17.7857, 95% C.I. 4.4847, 70.5361). A cohort comprising 24% of the women with fetal malformations in their initial pregnancies seemed to be intrinsically vulnerable to fetal malformation during successive pregnancies: when their seizure disorder type had been recorded all had genetic generalized epilepsies, compared with a 45.8% generalized epilepsy rate in women with initial but not subsequent pregnancy malformations (P = 0.0121). CONCLUSIONS: If fetal malformation had occurred in an initial ASM-treated pregnancy there was a significantly increased hazard of fetal malformation in the subsequent pregnancy, particularly if the woman involved had a genetic generalized epilepsy.
Assuntos
Anormalidades Induzidas por Medicamentos , Epilepsia Generalizada , Epilepsia , Complicações na Gravidez , Anticonvulsivantes , Austrália , Feminino , Humanos , Gravidez , Sistema de RegistrosRESUMO
OBJECTIVES: To investigate possible factors that influenced whether pregnancy in women with epilepsy resulted in the desirable outcome of a live-born non-malformed infant and a mother whose pregnancy had been seizure free. RESULTS: The desirable outcome, as defined, occurred in 46.3% of unselected pregnancies in the database of the Australian Register of Antiepileptic Drugs in Pregnancy (APR). The only factor investigated that had a statistically significant (Pâ¯<â¯0.05) effect, increasing the chance of such a desirable outcome, was freedom from seizures in the pre-pregnancy year. However, anti-seizure medication (ASM) doses, particularly valproate doses, had been reduced prior to 15.6% of the pregnancies, and this may have concealed factors that otherwise may have adversely affected the desirable outcome rate. Analysis of data for monotherapy with the more commonly used ASMs appears to suggest that employing levetiracetam at the outset of antiseizure therapy may offer a better chance of a desirable outcome to future pregnancies than monotherapy with other ASMs, but this finding is not confirmed statistically. CONCLUSIONS: In pregnancies where valproate use has already been minimized, seizure control throughout the pre-pregnancy year was associated with the best chance of a desirable outcome, as defined above. In most Australian women starting therapy for epilepsy initiating treatment with levetiracetam monotherapy may offer the best chance of such a desirable outcome to a future pregnancy, yet to be confirmed.
Assuntos
Epilepsia , Complicações na Gravidez , Anticonvulsivantes/uso terapêutico , Austrália/epidemiologia , Epilepsia/tratamento farmacológico , Feminino , Humanos , Levetiracetam/uso terapêutico , Gravidez , Complicações na Gravidez/tratamento farmacológico , Ácido Valproico/uso terapêuticoRESUMO
AIMS: Equations to calculate albumin-adjusted total concentrations have been validated to correlate with measured free concentrations for both phenytoin and valproate, but there is a lack of data to assess correlation with clinical outcomes. We aimed to assess the association of hypoalbuminaemia and albumin-adjusted total concentrations with concentration-dependent toxicity for phenytoin and valproate and review the impact on management decisions following concentration monitoring in hypoalbuminaemia. METHODS: Patients undergoing concentration monitoring for phenytoin or valproate between January and December 2018 were included. Patients were identified using a centralised laboratory database with data extracted from medical records. RESULTS: Total phenytoin concentrations were measured for 144 patients, with hypoalbuminaemia (≤30 g L-1 ) recorded in 59 (41%) patients. Albumin-adjusted phenytoin concentration >20 mg L-1 was associated with increased neurological adverse effects (77% vs. 43%, P < .001). On logistic regression, higher albumin-adjusted phenytoin concentration was an independent risk factor for neurotoxicity (OR 1.06, 95% CI 1.01-1.12, P = .011). Total valproate concentrations were measured for 383 patients, with hypoalbuminaemia (≤30 g L-1 ) noted in 53 (14%) patients. For the valproate cohort, hypoalbuminaemia (42% vs. 28%, P = .039) and albumin-adjusted valproate concentration >100 mg L-1 (49% vs. 23%, P < .001) were both associated with increased neurotoxicity. On multiple logistic-regression, valproate daily dose (aOR = 1.01, 95% CI 1.00-1.02, P = .006) and albumin-adjusted valproate concentration (aOR 1.01, 95% CI 1.00-1.02, P = .033) were independent risk factors for neurotoxicity after accounting for confounders. CONCLUSION: While measuring free drug concentrations in hypoalbuminaemia would be ideal, the adjustment equations can help identify vulnerable patients needing further assessment of potential concentration-dependent toxicity.
Assuntos
Hipoalbuminemia , Ácido Valproico , Estudos de Coortes , Humanos , Fenitoína/efeitos adversos , Estudos Retrospectivos , Ácido Valproico/efeitos adversosRESUMO
OBJECTIVE: To ascertain whether epileptic seizure control during pregnancy differed between Australian women with previously surgically treated epilepsy, and those with only medically treated epilepsy. MATERIALS/METHODS: Analysis of data for 74 pregnancies of women with surgically treated focal epilepsy, compared with that from 1013 pregnancies in women with medically treated focal epilepsy, both groups drawn from the Australian Register of Antiepileptic Drugs in Pregnancy between 1999 and 2020. RESULTS: Seizures of all types, and also convulsive seizures, were less well controlled during pregnancy in the previously surgically treated cases, the difference for seizures of all types (68.9% versus 50.1%) being statistically significant (p < .05). This result was contrary to the outcome of a previously published study of the same question carried out in India. CONCLUSIONS: At present, it may be premature to conclude that previous epilepsy surgery will be associated with a better chance of seizure-free, or seizure-controlled, pregnancy.
Assuntos
Epilepsia , Complicações na Gravidez , Anticonvulsivantes/uso terapêutico , Austrália/epidemiologia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/cirurgia , Feminino , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/cirurgia , Resultado da Gravidez/epidemiologia , Convulsões/tratamento farmacológicoRESUMO
PURPOSE: To assess the possible contribution of factors in additional to intrauterine anti-seizure medication (ASM) exposure in the occurrence of fetal malformation in women with ASM-treated epilepsy. RESULTS: Logistic regression analysis showed that maternal age over 31 years, family histories of fetal malformation, and conception after assisted fertility treatment, and also dosage of valproate, carbamazepine, and topiramate, made statistically significant (P<0.05) contributions to the fetal malformation rate in 2223 pregnancies in Australian women with epilepsy. The malformation rates were lower in pregnancies where the non-ASM-associated contributory factors were not present: statistically significantly so for all ASM-exposed pregnancies, and those pregnancies exposed to the more potent teratogenic drugs. CONCLUSION: It is important to consider the possible roles of identified, and also possible non-identified, non-ASM factors in relation to the occurrence of fetal malformations in the pregnancies of women with ASM-treated epilepsy.
Assuntos
Anormalidades Induzidas por Medicamentos , Epilepsia , Complicações na Gravidez , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Anticonvulsivantes/efeitos adversos , Austrália/epidemiologia , Epilepsia/tratamento farmacológico , Feminino , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Ácido Valproico/efeitos adversosRESUMO
OBJECTIVES: To examine factors contributing to failure to achieve full seizure control during pregnancy in women with anti-seizure medication (ASM) treated generalized epilepsy compared with focal epilepsy. RESULTS: Full seizure control was not attained in 51.4% of 1223 pregnancies of women with focal epilepsies in the Australian Pregnancy Register, and in 38.7% of 1026 pregnancies in women with generalized epilepsy (Pâ¯<â¯0.05). For convulsive seizures only, the corresponding figures of 20.8% and 22.9% were reasonably similar. Where seizures had occurred in the pre-pregnancy year, 82.5% of the focal epilepsy pregnancies were seizure affected, and 70.1% of the generalized epilepsy ones (Pâ¯<â¯0.05). Where the pre-pregnancy year was seizure free, the corresponding figures were 22.6% and 16.4% (Pâ¯<â¯0.05), a roughly four-fold lower rate. Maternal age, epilepsy onset age, and epilepsy duration also differed between the focal and generalized epilepsy pregnancies. Multivariate regression analysis showed that generalized epilepsy and younger maternal age were associated with statistically significant decreased risks of seizure-affected pregnancy, and having seizure-affected pre-pregnancy years with an increased risk. However, for convulsive seizures only, the risk of seizure-affected pregnancy appeared increased in generalized epilepsy. CONCLUSIONS: The risk of seizure-affected pregnancy appears lower in women with generalized epilepsy, independently of pre-pregnancy seizure control, itself a major determinant of the risk. The risk of having only convulsive seizures in pregnancy was not lower in generalized epilepsy than in focal epilepsy. ASM therapy seemed less effective in controlling focal than generalized epileptic seizures during pregnancy.
Assuntos
Epilepsias Parciais , Epilepsia Generalizada , Anticonvulsivantes/uso terapêutico , Austrália , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Feminino , Humanos , Gravidez , Convulsões/tratamento farmacológico , Convulsões/epidemiologiaRESUMO
OBJECTIVE: To determine whether there is a relationship between folic acid dose and the degree of protection against valproate-associated and other antiepileptic drug (AED)-associated fetal structural malformations in women with AED-treated epilepsy. METHODS: Statistical analysis of data from the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy involving 2104 folic acid-treated pregnancies in women with epilepsy. RESULTS: Multiple variable logistic regression failed to demonstrate any statistically significant effect of folic acid dosage in reducing overall fetal malformation rates in women taking folic acid either before and during pregnancy (Pâ¯=â¯0.640) or during early pregnancy only (Pâ¯=â¯0.801), and in reducing spina bifida occurrence rates (Pâ¯=â¯0.409). CONCLUSIONS: In the present state of knowledge, it would seem misguided to hope that a folic acid dose of 5â¯mg/day taken before and during pregnancy would protect against the occurrence of valproate-associated and other AED-associated fetal structural malformations. Future studies are required to determine whether high-dose periconceptional folate use may decrease the risk of other valproate-associated adverse fetal outcomes, including impaired post-natal neurobehavioral development.
Assuntos
Anormalidades Induzidas por Medicamentos , Complicações na Gravidez , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/efeitos adversos , Austrália , Feminino , Ácido Fólico , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Ácido Valproico/efeitos adversosRESUMO
OBJECTIVE: To assess the outcomes in women with epilepsy in relation to fetal malformation and epileptic seizure control during pregnancy when valproate (VPA) intake was ceased, or the drug's dose was reduced before pregnancy. METHODS: Statistical analysis of data collected in the Australian Pregnancy Register between 1999 and 2018 concerning 580 pregnancies previously treated with VPA, with the VPA dose reduced or the drug withdrawn prior to pregnancy in 158 cases. RESULTS: Although the available data have limitations, fetal malformation rates in the pregnancies studied were lower in the VPA changed pregnancies (4.5%) than in the VPA unchanged comparator pregnancies (10.9%, hazard ratio [HR] 0.412, 95% confidence interval [CI] 0.190-0.892), and were only 2.7% where VPA intake was ceased before pregnancy (HR 0.262, 95% CI 0.083-0.826). Seizure-affected pregnancies were more frequent in the VPA changed pregnancies than in the VPA unchanged ones (46.2% vs 30.8%, HR 1.500, 95% CI 1.203-1.870). Convulsive seizure-affected pregnancies also were increased, but the difference was not statistically significant. SIGNIFICANCE: Prepregnancy reduction in VPA dosage reduced the hazard of fetal malformations, whereas ceasing intake of the drug decreased the hazard to one similar to that which applies in the general population, but at a cost of decreased control of epileptic seizures during the pregnancies studied. Further investigations are needed to see whether such findings apply more widely in women with epilepsy.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/efeitos adversos , Epilepsia/complicações , Complicações na Gravidez/tratamento farmacológico , Ácido Valproico/efeitos adversos , Anormalidades Induzidas por Medicamentos/epidemiologia , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Austrália/epidemiologia , Epilepsia/tratamento farmacológico , Feminino , Humanos , Gravidez , Sistema de Registros , Convulsões/complicações , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Convulsões/prevenção & controle , Ácido Valproico/administração & dosagem , Ácido Valproico/uso terapêuticoRESUMO
OBJECTIVE: We report data from the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) to see if there are significant differences in relation to the courses and outcomes of the twin pregnancies contained in the register, as compared with the singleton ones. METHODS: The APR has been under the oversight of Melbourne institutional Human Ethics Research Committees; all women enrolled in the APR have provided written informed consent. Data from the APR were transferred to a spreadsheet and then analyzed using simple statistical techniques including logistic regression. RESULTS: The population studied comprised 44 twin and 2261 singleton pregnancies; thus, twin pregnancies accounted for 1.91% of all pregnancies studied. The women carrying twins tended to be older than the women with singleton pregnancies to a statistically significant extent, their pregnancies more often originated from assisted fertilization techniques, and their babies were more often delivered by cesarean section. There were no statistically significant differences in relation to antiepileptic drug (AED) therapy. Individual twins had statistically significantly lower mean birthweights than singleton babies and they were statistically significantly more often involved structurally malformed foetuses. In the first year of life, the twin pregnancies statistically significantly more often produced offspring that were affected by seizures in infancy. SIGNIFICANCE: The data suggest that there may be an increased hazard of fetal malformation in the offspring of twin pregnancy in women with epilepsy, but that with contemporary standards of management of epilepsy and pregnancy, there is unlikely to be an increased hazard of seizure-affected pregnancy.
Assuntos
Epilepsia/complicações , Complicações na Gravidez/patologia , Gravidez de Gêmeos , Austrália/epidemiologia , Estudos de Casos e Controles , Cesárea/estatística & dados numéricos , Anormalidades Congênitas/epidemiologia , Feminino , Humanos , Gravidez , Resultado da Gravidez , Gravidez de Gêmeos/estatística & dados numéricos , Sistema de RegistrosRESUMO
OBJECTIVES: To assess (a) the incidence of seizures in the first year of life in infants born to mothers with epilepsy and (b) factors that might contribute to the seizure incidence. MATERIALS & METHODS: Analysis of data collected in the Australian Register of Antiepileptic Drugs in Pregnancy during and at the end of the year after pregnancy. RESULTS: By the end of a year following pregnancy, seizures had occurred in the progeny of 47 pregnancies (2.40%), including febrile seizures in 18 (0.92%), the latter rate being higher than the 0.40% and 0.59% rates for the same situation in the general population reported in the recent literature. Seizures in infancy were more likely in the offspring of mothers with generalized as compared with focal epilepsies (3.65% vs 1.56%; RR = 2.332; P < .05) and within the generalized epilepsy mothers in those who were not seizure free during pregnancy (4.83% vs 2.89%). Seizures were also more likely in infants with foetal malformations, especially ones not discovered until after the first post-natal month. CONCLUSIONS: These findings may help in advising mothers with epilepsy regarding the chance of their offspring experiencing seizures in the first year of life; they also suggest the desirability of achieving maternal seizure control throughout pregnancy.
Assuntos
Epilepsia/complicações , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/etiologia , Complicações na Gravidez , Convulsões/epidemiologia , Adulto , Austrália/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , GravidezRESUMO
OBJECTIVES: To assess the possibility that the occurrence of seizures or the use of antiepileptic drug (AED) therapy might have influenced the rate of occurrence of volunteered histories of patient-recognized depression during pregnancy in women with epilepsy. MATERIALS AND METHODS: Analysis of data from 2039 pregnancies in the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) followed during pregnancy and to the end of the year after its end. RESULTS: Patient-recognized depression occurrence rates during pregnancy were a little lower rather than higher in seizure-affected than in seizure-free pregnancies (5.67% vs 6.41%), though higher in AED-treated than AED-untreated pregnancies (6.24% vs 5.26%; RR = 1.185, 95% CI 0.612, 2.295). Logistic regression analysis showed that carbamazepine dosage had a statistically significant relationship with a decreasing rate of patient-recognized depression occurring during pregnancy and topiramate dosage with an increasing rate. CONCLUSIONS: Carbamazepine and topiramate both have established potentials for causing teratogenesis, and it is possible that replacement of carbamazepine with a less teratogenic AED, for example levetiracetam, might result in any subsequent depression that occurs in pregnancy being inappropriately attributed to the newly introduced agent.
Assuntos
Anticonvulsivantes/uso terapêutico , Depressão/epidemiologia , Epilepsia/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Adulto , Austrália , Carbamazepina/uso terapêutico , Feminino , Humanos , Levetiracetam/uso terapêutico , Gravidez , Convulsões/tratamento farmacológico , Topiramato/uso terapêuticoRESUMO
Data from 2182 pregnancies in the Australian Register of antiepileptic drugs in pregnancy that were followed to term, with 1965 followed for another year, were analyzed to ascertain whether preexisting illness influenced i. the hazard of fetal malformations, and ii. seizure control during pregnancy. Fetal malformation occurred in 74 of the 842 pregnancies associated with preexisting illness (8.8%) and in 84 of the 1340 comparator pregnancies (6.27%), Relative Risk (R.R.)â¯=â¯1.402 (95% Confidence Interval (C.I.)â¯=â¯1.038, 1.893). Logistic regression showed statistically significant effects of preexisting maternal drug-treated psychiatric illness, untreated psychiatric illness, and use of citalopram, carbamazepine, valproate, and topiramate in increasing hazard of fetal malformation. Preexisting nonpsychiatric illness and other antiepileptic drugs and drugs prescribed for psychiatric illness, mainly antidepressants, had no such effect. Seizures occurred during 405 of the 842 pregnancies associated with preexisting illness, and during 593 of 1340 comparison pregnancies (48.1% v 44.3%; R.R.â¯=â¯1.087; 95% C.I.â¯=â¯0.991, 1.192). There were no statistically significant relationships between preexisting nonpsychiatric and psychiatric illnesses separately and seizure control during pregnancy. Thus, apart from consequences of antiepileptic drug exposure, preexisting maternal psychiatric illness, in its own right, or when treated with citalopram, appears to be associated with increased hazards of fetal malformation.
Assuntos
Anticonvulsivantes/efeitos adversos , Antidepressivos/efeitos adversos , Anormalidades Congênitas , Epilepsia , Transtornos Mentais , Complicações na Gravidez , Sistema de Registros , Convulsões , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Austrália/epidemiologia , Anormalidades Congênitas/epidemiologia , Anormalidades Congênitas/etiologia , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Humanos , Transtornos Mentais/complicações , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Convulsões/tratamento farmacológico , Convulsões/epidemiologiaRESUMO
We investigated the outcome of altering antiepileptic drug (AED) therapy in the year before pregnancy on 2233 occasions in Australian women in the 20-year period of functioning of the Raoul Wallenberg Australian Pregnancy Register (APR). Therapy had been altered in 358 instances (16%) in the months prior to the pregnancy (median interval: 18â¯weeks). Antiepileptic drug doses had been changed in 141 pregnancies (39.4%), being decreased in 94; drugs changed in 151 (42.2%); drugs withdrawn without replacement in 66 (18.4%) but resumed in 40 before pregnancy ended. The main drugs involved were valproate (34%), phenytoin (16.5%), topiramate (12.6%), and carbamazepine (11.4%). Antiepileptic drug doses were increased significantly more often (16.9% vs. 6.4%) when epilepsy before pregnancy was not controlled, and AED treatment ceased significantly less often (13.6% vs. 24.0%). The alterations were more often made in women with generalized epilepsies and in those whose seizure disorders were not fully controlled in the prepregnancy year, suggesting that avoidance of teratogenicity and achieving improved seizure control often motivated the changes. Overall, the alterations did not result in improved rates of seizure freedom during pregnancy, as compared with pregnancies where therapy was unchanged; however, fetal malformation rates were lower 3.6% vs. 5.4%, but this difference did not attain statistical significance. The same trends regarding seizure control and malformations persisted after pregnancies involving valproate exposure were excluded. In conclusion, this analysis of the APR cohort did not demonstrate that altering AEDs before pregnancy produced a significant improvement in seizure control and the reduction in fetal malformation rate that occurred was not statistically significant.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Adulto , Austrália/epidemiologia , Estudos de Coortes , Epilepsia/epidemiologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/epidemiologia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To gain insight into the main advantages and disadvantages that might result from valproate being unavailable for women who intend to become pregnant. MATERIALS AND METHODS: Analysis of data from the Australian Pregnancy Register concerning pregnancies exposed to valproate (N = 501) and pregnancies where previous valproate intake had been ceased before pregnancy (N = 101). RESULTS: The risk of foetal malformation associated with valproate exposure during pregnancy was dose-related, and there was a tendency for the more major malformations, including those often managed by therapeutic abortion, for example spina bifida, to occur at higher valproate doses. Had there been no exposure to valproate during pregnancy, some 80% of the foetal malformations that occurred might have been avoided. Cessation of previous valproate therapy before pregnancy was associated with an increased hazard of seizure-affected pregnancy. This was particularly the case for women with generalized epilepsies, in whom the incidence of seizure-affected pregnancy was increased by 50% to nearly 100%. CONCLUSIONS: Avoiding valproate intake during pregnancy is likely to reduce the incidence of foetal malformation, but at a cost of worsened maternal epilepsy control. Individualization of treatment is particularly important in considering withdrawal of valproate in the light of the fact that it is much more widely used in generalized epilepsy, there being fewer alternative drugs than for focal epilepsy and withdrawal is not without risk for both mother and baby. This study may provide a quantitative basis for assessing the balance between benefit and disadvantage for individual women with valproate-treated epilepsy who are considering pregnancy.
Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Ácido Valproico/efeitos adversos , Adulto , Austrália/epidemiologia , Feminino , Humanos , Gravidez , Sistema de Registros , Risco , Convulsões/tratamento farmacológicoRESUMO
The literature suggests that cesarean delivery or birth is carried out more often in pregnant women with epilepsy (WWE) than in pregnant women in the general population. Data were utilized from the Australian Pregnancy Register (APR) for Women on Antiepileptic Medication to investigate this issue in Australia. Over almost two decades, the mean CS rate in 1900 APR women was 39.2%, but was only 29.9% in women in the general population (relative risk (R.R.)â¯=â¯1.31, 95% confidence interval (C.I.) 1.24, 1.39). Rates for forceps and suction-assisted delivery were similar in the two datasets. The 9.3% excess CS rate was almost entirely accounted for by operations carried out prior to the onset of labor. The rates for CS during labor were very similar. Only 11.0% of the WWE knew the indication for their prelabor CS, whereas 69.8% knew why theirs had been carried out during labor (odds ratio (O.R.)â¯=â¯0.054; 99% C.I. 0.032, 0.089). Slightly older mothers and increased proportions of primipara probably made small contributions to the increased prelabor CS rate in the Australian WWE, but most of the excess could not be accounted for in the Register data. Australian obstetricians may have tended to regard prelabor CS as a preferable course of action in managing delivery in WWE, even in the absence of other indications.