Cookies are small text files stored on the device you are using to access this website. For more information please take a look at our terms and conditions. Some parts of the site may not work properly if you choose not to accept cookies. To find relevant articles please visit here to pick a cluster. With appropriate dosage adjustment, there is little evidence of safety concerns for a woman taking antiepileptic drugs during pregnancy, but the foetus may be at risk of malformations and neurodevelopmental shortcomings.
The safety of antiepileptic drug use in pregnancy involves: This article focuses on these additional pregnancy-related safety aspects, and not with Graeme eadie wife sexual dysfunction extensive matters of antiepileptic drug safety in general. In recent years, antiepileptic drugs have been increasingly used in treating disorders other than epilepsy. So much so that Bobo et al.
In that study, antiepileptic drugs had been taken in 2. Therefore, antiepileptic drugs were taken for epilepsy by 0. Despite this considerable use for disorders other than epilepsy, nearly all the available scientific information relating to the clinical pharmacology of these drugs in pregnancy has been derived from studies on their use in women with epilepsy, and their employment in other disorders has depended on application of this experience.
Consequently, this article is mainly concerned with the use of these drugs in pregnant women who have epileptic seizure disorders. This article is based on a personal collection of the relevant English language literature, dating from Graeme eadie wife sexual dysfunction s, and on publications traced through the PubMed database, searched using the term antiepileptic drug, in combination with, individually, the terms: Some material drawn from the Australian Register of Antiepileptic Drugs in Pregnancy is also included.
Since this register includes pregnancies in women with epilepsy who did not take antiepileptic drugs in at least the earlier half of pregnancy, its data can be used Graeme eadie wife sexual dysfunction help discriminate between the effects of antiepileptic drug exposure itself and the combined effects of the drugs plus having epilepsy.
There appears to be little or no evidence that antiepileptic drug use in pregnancy produces additional safety concerns for the woman involved, beyond those that result from decreased control of her epileptic seizures. Reasonably effective antiepileptic drug treatment has been available sinceand there has been little published on untreated epilepsy in pregnancy for many years.
Half a century ago, the predominant view was that epileptic seizure control tended to deteriorate during pregnancy. However, the published studies, included in the review of Schmidt "Graeme eadie wife sexual dysfunction" not consistent in showing this. The interpretation of these relatively early studies and much of the subsequent data have often been confounded by issues relating to antiepileptic drug use and prescribed drug dosages.
Worsening control of epileptic seizures could expose the pregnant woman to risk of physical injury and possibly death during seizures, and there are reports of such events . However, in an increased mortality rate was found in pregnant women with epilepsy in the UK, mostly attributable to sudden unexplained death .
In addition to physical injury, loss of seizure control could lead to psychological harm to the woman with epilepsy, which may result in reduced social activities and opportunities and may impair her quality of life, particularly if seizures cause the loss of her driving
Graeme eadie wife sexual dysfunction, for example.
Since the mids, a number of studies have shown that, as pregnancy progresses, steady state plasma concentrations of antiepileptic drugs tend to fall unless the drug doses are increased . The factors involved Graeme eadie wife sexual dysfunction producing this fall appear to be: The extent of the decreases in plasma antiepileptic drug concentration caused by these factors varies between the individual drugs and the stage of pregnancy.
The decreases tend to be relatively small for agents that are cleared from the body predominantly by renal excretion unmetabolised, and are larger for drugs cleared mainly through biotransformation.
The greatest clearance increase among the currently commonly used antiepileptic drugs is that for lamotrigine, eliminated largely by N-glucuronidation.
Doses of this drug may need to be doubled or tripled during pregnancy to maintain steady-state plasma drug concentrations at their pre-pregnancy values. In contrast, the fall in plasma carbamazepine concentration tends to be relatively small and not statistically significant when the drug is used as the sole antiepileptic agent in pregnancy, but is appreciably when it is employed in combination with phenytoin or phenobarbitone .
The fall in plasma concentrations of valproate during pregnancy is also usually relatively small. It is generally accepted that seizure control tends to correlate with plasma antiepileptic drug correlations. This raises the possibility that, unless antiepileptic drug doses are adjusted, falling circulating concentrations of antiepileptic drugs in pregnancy may explain any deterioration in seizure control that occurs.
The clinical impression has developed that, if antiepileptic drug doses are adjusted during and after pregnancy, so that plasma drug concentrations are maintained at their pre-pregnancy Graeme eadie wife sexual dysfunction in the individual, seizure control is unlikely to deteriorate. This impression has been supported by recent studies in which a dosage adjustment policy, when applied to lamotrigine, seems to have avoided worsening seizure control in pregnancy .
This avoidance of loss of seizure control associated with appropriate adjustment of antiepileptic drug dosage during pregnancy might suggest that the state of pregnancy itself does not enhance seizure genesis. However, a recent investigation has produced some evidence that seizures increase during pregnancy in women with epilepsy who are not being treated with antiepileptic drugs . For practical purposes, the safety of antiepileptic drug therapy for pregnant women will probably not be endangered by consequences of loss of seizure control if "Graeme eadie wife sexual dysfunction" is careful management of antiepileptic drug dosages throughout, and after, pregnancy, guided when feasible by plasma antiepileptic drug concentration monitoring.
The available literature does not permit any easy distinction being made between the possible effects of loss of control of epilepsy, and those caused by its drug treatment, during the course of pregnancy.
There seem to be no unequivocally demonstrated effects. The violence of maternal convulsive seizures might be expected to increase the risk of intrauterine foetal damage, possibly causing miscarriage, placental abruption, retro-placental haemorrhage or premature birth.
However, there have been surprisingly few reports of such complications occurring that are associated with convulsive seizures during pregnancy. InJanz and Fuchs  found more miscarriages and stillbirths had occurred in antiepileptic drug-treated pregnancies than in the pregnancies of women with untreated epilepsy, though post-mature and premature births were not more frequent.
InSpeidel and Meadow  failed to find any increase in rates of miscarriage, pre-term birth and low birthweights in antiepileptic drug pregnancies and Annegers et al  arrived at a similar conclusion in relation to spontaneous abortions.
Stillbirth rates were not increased in the pregnancies of adequately treated women with epilepsy .
McPherson et al  also found no increase in stillbirths, or in premature births in women with epilepsy. Interestingly, in a large contemporaneous database there was no increase in spontaneous abortion rates in almost 1 million Danish pregnancies that occurred in women with antiepileptic drug-treated epilepsy  . However, in the same data set, there was an increased spontaneous abortion rate in pregnant women who took these drugs for disorders other than epilepsy, a
Graeme eadie wife sexual dysfunction that is difficult to explain.
Katz et al  noted a statistically significant increased rate of "Graeme eadie wife sexual dysfunction" sections in the pregnancies of women with epilepsy; at least the majority of whom were taking antiepileptic drugs. Borthen and Gilhus  described a similar finding and also noted an increased incidence of pre-eclampsia, gestational hypertension and induced labour. Graeme eadie wife sexual dysfunction, sometimes larger scale, studies have shown inconsistencies between such findings in relation to antiepileptic drug-treated pregnancies.
It is possible that the differences in reported outcomes regarding some of these matters reflect standard management practices in different institutions more than courses of action made desirable by actual events in individual pregnancies.
Overall, it seems reasonable to conclude that, in the considerable majority of instances, antiepileptic drug use in pregnancy probably does not adversely affect, or unduly complicate or endanger, the course of pregnancy, despite occasional reports to the contrary such as that of Rauenszaucher et al . The majority of reports have shown that there is a tendency for babies exposed to antiepileptic drugs in utero to be a little premature, small for gestation age and of lower than expected birth weight .
Their head circumferences also tends to be smaller, but by the age of two years the circumference values fall within the normal range for the population. Such outcomes of pregnancy are unlikely to have any significant overall deleterious consequence for foetal safety and subsequent well-being. The respective contributions from having epilepsy, and from taking drug treatment for epilepsy, to the origins of these abnormalities have not been clarified. However, Finnish population data exist that show increased neonatal death rates in association with previous in utero antiepileptic drug exposure with a further study reaching a similar conclusion .
The explanation for this increased death rate, and its relation to antiepileptic drug exposure in utero rather than to the mother suffering from epilepsy, are both unclear. The issue of foetal malformation associated with antiepileptic drug exposure during pregnancy began to arise soon after the thalidomide tragedy of the s.
The influential early study of Janz and Fuchs  in concluded that such drug exposure was unlikely to be responsible for foetal malformations.
This was despite there being a 1. Aftera series of publications began to appear, first comprising small case series before later including larger data collections. The majority provided evidence, though it was not always statistically significant, that there was an increased hazard of foetal malformation in infants born to mothers who had taken antiepileptic drugs during pregnancy originally mainly phenytoin, phenobarbitone, or a drug biotransformed to the latter.
view developed that, as a class, antiepileptic drugs were teratogens. However, unlike the situation in relation to thalidomide, which appears to have been responsible for a particular pattern of malformation, foetal exposure to antiepileptic drugs seemed to be associated with a considerable variety of structural maldevelopments in exposed foetuses.
The abnormalities ranged from comparatively trivial deformities of the skin or digits through significant, though potentially surgically remediable, malformations, such as cardiovascular abnormalities and facial clefts, to devastating and uncorrectable ones e. It seems rather doubtful whether these syndromes represent genuine discrete drug-specific entities. Degrees of teratogenicity for antiepileptic drugs: Based on Australian Pregnancy Register data and other literature, gradient of increasing teratogenicity for antiepileptic drugs for which sufficient statistical information is available.
The top group appears safe, for practical purposes, though the data for gabapentin are relatively scanty. The second group has been suspect, particularly phenobarbitone.
The third group appears to be dose-related teratogens, though not particularly potent ones, whereas valproate is a significant teratogen.
With the subsequent publication of larger data sets, including material collected in various antiepileptic drug pregnancy registers Graeme eadie wife sexual dysfunction in the UK, North America, Australia and Europe [EURAP] and in governmental and institutional databases, the situation regarding antiepileptic drug-associated foetal malformation has become clearer.
Nevertheless, significant deficiencies in knowledge remain. Without working systematically through each development in this area, one important point that has emerged is that foetal malformation is not a class effect that involves all antiepileptic drugs. There is now reasonably persuasive evidence that the degree of teratogenicity varies between different antiepileptic drugs see figure 1.