Management of Women with Epilepsy: Are Guidelines Being Followed? Results from Case-note Reviews and a Patient Questionnaire

Authors


Address correspondence and reprint requests to Dr. M.T. Kampman at Department of Neurology, University Hospital of North Norway, 9038 Tromsø, Norway. E-mail: Margitta.Kampman@unn.no

Abstract

Summary: Purpose: Several international guidelines for the management of women with epilepsy (WWE) have been developed since 1989. We aimed to determine whether guidelines for the management of WWE are followed and whether active implementation of such guidelines makes a difference to clinical practice.

Methods: The study covered a 2-year period of “passive dissemination” of guidelines followed by a 2-year period of “active implementation.” Documentation reflecting adherence to the guidelines was abstracted retrospectively from electronic medical records on 215 WWE aged 16–42 years. Data abstracted from case notes included counselling on contraception and pregnancy-related issues; follow-up during pregnancy; advice on supplementation of folic acid, calcium, and vitamin D; and serum folate measurements. A questionnaire assessing the knowledge of WWE issues was completed by 112 (71%) of 157 patients.

Results: Documentation that WWE issues had been addressed was found in approximately one third of medical case records with no measurable effect of active implementation. Only the follow-up during pregnancy seemed to have improved. Serum folate measurements in 51 women treated with enzyme-inducing antiepileptic drugs (AEDs) revealed folate deficiency in 11 (22%). Respondents to the questionnaire recalled having received information from their neurologists on the interaction between AEDs and oral contraceptives (46%), need to plan pregnancy (63%), and folic acid requirement (56%).

Conclusions: Judged by a review of documentation in case notes, active implementation of guidelines had no measurable effect on clinical practice. However, the follow-up during pregnancy seemed to have improved. Patients' knowledge of WWE issues compared favorably with published studies. Better strategies are needed to secure successful implementation of guidelines.

Treating women of childbearing potential with antiepileptic drugs (AEDs) involves responsibility for fertility-related issues and nutritional requirements. The first international guidelines to assist physicians caring for women with epilepsy (WWE) were presented in 1989 (1). Subsequently in 1999, a review article on the subject was published in the Journal of the Norwegian Medical Association (2). This journal is distributed to 94% of all practicing physicians in Norway.

Despite publication of guidelines, several studies have found the care for WWE to be suboptimal (3–7). Methods of implementation that increase the likelihood of guidelines being used include reminders, interactive educational meetings, audit and feedback, patient-directed interventions, and development of local consensus. It is not known which guideline dissemination and implementation strategies are likely to be efficient under different circumstances (8). We introduced local guidelines and actively pursued their implementation, by using strategies that were feasible within the existing resources in our hospital.

For chronic conditions like epilepsy, the time between the care provided and its outcome can be long, and a poor outcome (e.g., major malformations in offspring or oral contraceptive failure) does not occur every time an error or deficiency occurs in the provision of that care. In this situation, details of practice (process data) provide more sensitive measures of quality than do outcome data (9). Patients' knowledge on WWE issues can serve as a surrogate outcome measure.

The aim of this study was to establish the degree of adherence to guidelines for the care of WWE before and after their active local implementation and assess their impact on the clinical practice by using case-note reviews and a patient questionnaire.

METHODS

Identification of patients and data collection

The Department of Neurology at the University Hospital of North Norway manages >95% of WWE older than 15 years in a population of 225,000. All women aged 16 to 42 years treated for epilepsy between 1 November, 1999, and 31 October, 2003, were included in the study. A subgroup of women of “child-raising potential” was defined excluding women with no childbearing potential (infertile and sterilized women) and women with no child-raising potential (considerably mentally retarded women and women diagnosed with malignancies). Retrospective collection of data from electronic patient records was approved by the Norwegian Social Science Data Services.

Guideline implementation

The study covered a 2-year period of “passive dissemination” of guidelines (i.e., publication of international and national guidelines) followed by a 2-year period of “active implementation” (Table 1). During the period of active implementation, a condensed local recommendation (Table 2) was developed, based on the first Norwegian review of management issues for WWE (2) as well as the national recommendations for folic acid intake in women of childbearing age (10) and for the treatment of osteoporosis (11). Advice on interaction between lamotrigine (LTG) and oral contraceptives (12) was added as it became available. Feedback was given to the medical staff on the audit results from the period of passive dissemination.

Table 1. Implementation of guidelines
Period of passive dissemination
 1989First international guidelines for care of WWE published (1)
 1998National recommendation on folic acid intake in women of childbearing age (10)
 September 1999First Norwegian review of guidelines for WWE (2)
 2001National recommendation for treatment of osteoporosis (11)
Period of active implementation
 1 November 2001Presentation of local recommendations (see Table 2) at an interactive educational meeting by one of the authors
 (M.T.K.)
Local recommendations and patient information on vitamin requirements made available on Internet and in print
Patient education handouts placed in waiting room
 June 2002Presentation of audit results (period of passive dissemination) to medical staff in the Neurology Department
Repeated presentation of local recommendations
 February 2003Questionnaire mailed to patients
Table 2. Local recommendations
 AEDRecommendation
  1. OC, oral contraceptive; CBZ, carbamazepine; FBM, felbamate; GBP, gabapentin; LEV, levetiracetam; LTG, lamotrigine; OXC, oxcarbazepine; PB, phenobarbital; PHT, phenytoin; PRM, primidone; TGB, tiagabine; TPM, topiramate; VPA, valproic acid; ZNS, zonisamide.

  2. aOnly higher doses.

  3. bChanged in 2002 (before: “no interactions with OCs”).

  4. cThose not wishing to take several supplements are advised to take at least a multivitamin tablet daily (0.2 mg folic acid and 200 IU vitamin D).

Fertility-related issues
 ContraceptionCBZ, FBM, OXC,a PB, PHT, PRM, TPMaAvoid OCs. If used, OCs should contain ≥50 μg of estrogen
LTGMeasure plasma concentration after start/stop OC (may decrease/increase)b
GBP, LEV, TGB, VGB, VPA, ZNSNo interactions with OCs
Planned pregnancyAllPreconceptional counseling of all WWE of child-raising potential
Folic acid supplement 0.4 mg dailyAllBefore conception and throughout pregnancy
 4 mg dailyCBZ, VPABefore conception and in first trimester
Extended antenatal screeningAllGenetic counseling. High-level ultrasound week 12–14 and 17 of gestation. Amniocentesis if ultrasound equivocal or not available
Vitamin KPB, PHT, PRM, CBZ10 mg daily, final month of pregnancy
Nutritional requirements
 Folic acidCBZ, PB, PHT, PRM, VPASupplement 0.4 mg dailyc
 Vitamin DCBZ, PB, PHT, PRMDaily intake of vitamin D, 800 IU, and calcium, 1,500 mgc

Case-note review

Abstracted data included patient characteristics and measures of adherence to the guidelines: means of contraception documented or choice of contraceptive discussed; need to plan pregnancy mentioned; need for periconceptional folic acid supplementation mentioned; need for general folic acid supplementation mentioned; need for vitamin D and calcium supplements mentioned; and serum folate measurements. Detailed data were collected on the follow-up of 28 pregnancies.

Patient questionnaire

A one-page questionnaire (Table 3) was mailed to 157 of 169 WWE who were seen by a neurologist during the period of passive dissemination (five patients with malignant disease were excluded, and another seven were not yet registered in the database).

Table 3. Patient questionnaire
Have you heard that …NoYes,
in the Dept. of
Neurology

Yes,
elsewhere
… all women who can become pregnant should use a folate supplement every day?
… oral contraceptives can fail if taken in combination with AEDs?
… other medication (including oral contraceptives and herbal medicine) can change the effectiveness of AEDs?
… women taking AEDs should contact their neurologist when planning pregnancy?
… women who use certain AEDs could be at higher risk of osteoporosis?
Where did you get the information that you have obtained “elsewhere”? (more than one answer possible)
□ General practitioner            □ Internet
□ Gynecologist               □ Brochures
□ Pharmacy                □ Family or friends
□ Epilepsy society              □ Other ______________________
Magazines, radio, television
 Do you use nutritional supplements?Every daySometimesNever
 Multivitamins
 Folic acid
 Cod liver oil
 Fish oil
 Calcium
 Other ______________________
Do you require contraception?□ Yes □ No
In case you do, what type of contraception have you used during the past year?
□ Oral contraceptive, brand name __________      □ Condom
□ Depo-Provera                  □ Intrauterine contraceptive device
□ I am/my partner is sterilized              □ Other ______________________

RESULTS

Demographic and treatment data

In total, 215 electronic medical records were included in the case-note review. One hundred sixty-nine women attended the Department of Neurology in the period of passive dissemination, 176 in the period of active implementation, and 130 (60%) during both periods. Patient characteristics are summarized in Table 4. The proportion of women with child-raising potential was higher among patients who responded to the questionnaire (90%) than in the total population studied (77%).

Table 4. Patient characteristics
 Women of
child-raising
potential
(n = 165)
Women with no
child-raising
potential
(n = 50)
  1. AED, antiepileptic drug.

Mean age30 yr30 yr
Duration of treatment
 Mean11 yr15 yr
 >5 yr11167%4080%
 >10 yr 8149%3672%
 Monotherapy12777%3162%
 Polytherapy >2 AEDs  3 2% 510%

Fertility-related issues

Documentation that the respective fertility-related issues had been discussed at least once during the total study period was found in approximately one third of case notes (Table 5). The proportions were actually higher (26–29%) in the period of passive dissemination than in the period of active implementation (20–26%).

Table 5. Proportion of case notes containing documentation that fertility-related issues and nutritional requirements had been discussed
 Period of passive
dissemination
Period of active
implementation
Total study period
At least onceMore than once
  1. “n” for subgroups refers to the total study period.

  2. aWomen taking AED known to interact with oral contraceptives.

  3. bAnalysis limited to women taking AED known to interact with folate metabolism (cf. Table 2).

  4. cAnalysis limited to women taking AED known to interact with bone metabolism (cf. Table 2).

Fertility-related issues
Use of contraception
 Women of child-raising potential (n = 165)29%25%35% 8%
 Women at risk of OC failurea (n = 82)26%26%33% 5%
Importance of planning pregnancy (n = 165)29%20%33% 9%
Nutritional requirements
 Folic acid
   Women of child-raising potential (n = 165)25%24%34%10%
   Women of no child-raising potentialb (n = 42)20% 8%21% 7%
Bone health
  Women of child-raising potentialc (n = 70) 0% 5% 4% 0%
  Women of no child-raising potentialc (n = 37) 6% 7% 8% 3%

Only three women had used an oral contraceptive that contained ≥50 μg of the estrogen component. Five oral contraceptive failures were documented in 62 women treated with carbamazepine (CBZ), three of which resulted in termination of the pregnancy. During the last year of the study period, 31 women of child-raising potential used LTG. Three women had received information on the interaction between LTG and oral contraceptives (correct in two cases, erroneous in the third).

Pregnancies

Data on 28 pregnancies abstracted from the case notes are summarised in Table 6. Pregnancy-related issues had been discussed before conception with 65% of these women. During the period of active implementation, notes on pregnant women appeared to be more detailed than those during the period of passive dissemination.

Table 6. Pregnancy data
 Period of passive dissemination
(n = 17)
Period of active implementation
(n = 11)
  1. aDependent on AED taken, as specified in Table 2.

  2. bOnly women treated with enzyme-inducing AED (period of passive dissemination: n = 6; period of active implementation: n = 4).

  3. cMeningomyelocele (diagnosed prenatally) and biliary atresia (diagnosed postnatally).

Planned pregnancy65%64%
OC failure018%
Monotherapy88%82%
Folic acid
 0.4 mg daily ≥4 wk before conception88%64%
 Recommended dosea≥4 wk before conception59%55%
 Recommended dosea in first trimester53%82%
Genetic counseling and high-level ultrasound47%73%
Vitamin Kb83%75%
Major malformations2c0

Nutritional requirements

Information on folic acid supplementation was documented in 34% of women of child-raising potential and in 21% of women considered to have no child-raising potential (see Table 5). No more than 5% of women treated with hepatic enzyme–inducing AEDs had received information about vitamin D and calcium requirements (see Table 5).

Serum folate measurements

Serum folate levels below the cutoff value (<5 nM) were found in 11 (22%) of 51 patients taking enzyme-inducing AEDs and in none of 24 taking valproic acid (VPA). Documentation of folic acid supplementation was available for 49 (65%) of 75 patients. None of the patients supplementing ≥0.2 mg of folic acid daily (n = 21) were folate deficient.

Patient questionnaire

Questionnaires were returned by 112 (71%) of 157 women. Results from the questionnaire regarding patients' knowledge on WWE issues are summarised in Table 7. Sources of information, apart from neurologists, were general practitioners (41%), written patient information material (40%), friends and relatives (39%), media (32%), patient organizations (25%), and the Internet (15%).

Table 7. Questionnaire data


Have you heard that …
Yes,
from my
neurologist
Yes, from
another
sourcea


No
  1. aSources of information, apart from neurologists, were general practitioners, written patient information material, friends and relatives, media, patient organisations, and the Internet.

  2. Data were analyzed for the appropriate subgroups: bwomen of child-raising potential; cwomen of child-raising potential taking AEDs that interact with oral contraceptives (cf. Table 2); dall women (independent of child-raising potential) taking AEDs that interact with bone metabolism (cf. Table 2).

… WWE should contact their neurologist when planning pregnancy? (n = 94b)63%14%23%
… oral contraceptives can fail if taken in combination with AEDs? (n = 56c)46%25%29%
… all women who can become pregnant should use a folate supplement every day? (n = 94b)56%18%26%
… WWE who use certain AEDs could be at higher risk of osteoporosis? (n = 43d)5%7%88%

Seventy women needed contraception, including the four youngest respondents (all 17 years old). Twenty-five women used hormonal contraception (seven of them were taking interacting AEDs), 20 had intrauterine devices, 18 used condoms, and two used other contraceptive methods. Five women were sterilized. In the subgroup of women treated with enzyme-inducing AEDs, 40 (71%) of 56 knew that oral contraceptives can fail if taken in combination with AEDs. Twenty-six (46%) had received this information from their neurologist. Three of seven women using enzyme-inducing AEDs and oral contraceptives were not aware of possible interactions, and only one woman used a high-estrogen oral contraceptive. Need for contraception was reported by 20 (80%) women treated with LTG; eight of them used oral contraceptives.

DISCUSSION

Implementing WWE guidelines has proven to be difficult (3–7,13), even when considerable effort was made (14). In our study, documentation that WWE issues had been addressed was found in approximately one third of medical records. We found no evidence of change in clinical practice that could be related to implementation of local guidelines. Only follow-up during pregnancy seems to have improved and compares favorably with other published studies (3,6). However, poor documentation of adherence to guidelines does not necessarily mean poor quality of care. Patients who completed the questionnaire reported to have received information more often than is documented in case notes, and their knowledge compares favorably with that in other studies (5–7).

Measuring adherence to guidelines

Access to complete electronic case notes of all WWE from an unselected patient population is the major strength of this study. Supplementing these data with a patient questionnaire provides a reasonable picture of the care provided.

Case-note review

By reviewing case notes, it is possible to assess whether the variable of interest was documented, but not necessarily whether the information provided was correct and understood by the patient. The case notes are medicolegal documents as well as an important means of communication between specialists and general practitioners. Therefore although not everything that is discussed during a consultation between physician and patient is documented in notes, the central issues are likely to be mentioned.

Questionnaire

While previous surveys had relatively low response rates [31 and 57% (5,7)], 71% of the questionnaires were returned in this study. The favorable results on patients' knowledge of WWE issues may be due to the respondents being more interested in WWE issues than were nonrespondents.

Fertility-related issues

Actively implementing guidelines had no measurable effect on the clinical practice concerning fertility-related issues, although this finding may have been influenced by patients who did not receive repeated advice at repeated visits.

It is encouraging that more than half of the respondents recalled having discussed fertility-related issues with their neurologists. Counseling patients with no child-raising potential about fertility-related issues is important as they enter the reproductive age, but repeating and reinforcing this information during subsequent visits may not always be appropriate. Therefore this group was excluded from analyses concerning fertility-related issues. Four youngest respondents of the questionnaire were sexually active, and one mentally retarded woman with no child-raising potential gave birth to a child, underscoring the need to counsel all women in an adult neurology service about fertility-related issues.

Contraception

Unplanned pregnancies may carry additional risks for WWE, and treatment with several AEDs increases the risk of oral contraceptive failure (15). Results of the questionnaire survey showed that many women used unreliable contraceptive methods. We found documentation of five oral contraceptive failures in the case notes, but actual numbers may be higher, as women not suspecting interactions between oral contraceptives and AEDs may not tell their neurologists if they experience oral contraceptive failures. Fairgrieve et al. (6) reported oral contraceptive failures to be the cause of one in four unplanned pregnancies in WWE. Seventy-one percent of the respondents treated with enzyme-inducing AEDs were aware of possible reduced efficacy of oral contraceptives, which is higher than reported previously [49% (5) and 59% (7)]. The proportion of women who answered that they had received this information from their neurologists (46%) was higher than documented in the case notes (33%), and a considerable number of women (25%) had received this information from other sources.

LTG does not reduce the efficacy of oral contraceptives, but LTG plasma levels are decreased significantly by oral contraceptives (12). Only two of 31 patients treated with LTG had received correct information on the interaction with oral contraceptives.

Preconceptional counseling is an integral part of published guidelines. The proportion of patients who were aware of the need for prepregnancy planning (77%) was about twice as high as reported by others (5–7).

Periconceptional folic acid supplementation

WWE should receive folic acid supplementation at least at dosage levels recommended for the general population, although this may not be enough for AED-treated women who do not metabolize folate effectively (15). Seventy-five percent of respondents in our study knew that all women who can become pregnant should use folic acid supplement, and the majority had learned this from their neurologists. In a British survey performed in 2000, only 38% of pregnant women recalled receiving advice on taking folic acid before conception and during early pregnancy (7).

Pregnancies

Guidelines contain detailed recommendations concerning pregnancy-related issues. In the notes on women who became pregnant, the need to plan a pregnancy and the need for periconceptional folic acid supplementation had been documented twice as often as in the total group. It is likely that the pregnancy-related issues were discussed mostly on the patient's initiative. In general, we had the impression that notes on pregnant WWE were more complete during the period of active implementation of guidelines.

The number of planned pregnancies (64%) in our small sample seems to be higher than reported from interviews of 300 pregnant women (44%) (6). The proportion of women who had used a folic acid supplement ≥4 weeks before conception and in the first trimester (79%) was much higher than in the general population in North Norway (7%) (16) and among British WWE (11%) (6). Two patients who gave birth to children with major malformations had used folic acid periconceptionally (see Table 6). The number of women who had received genetic counselling compares well with that in an earlier study (3). Use of high-level ultrasound, as recommended in the guidelines, increased from 47% in the first 2 years to 73% in the second half of the study. This finding probably reflects the improved perinatology service in our hospital since March 2001. Local guidelines recommend vitamin K supplementation in the last month of pregnancy in WWE treated with hepatic enzyme–inducing AEDs. Eight of 10 pregnant patients taking enzyme-inducing drugs received vitamin K supplement as recommended, which is considerably higher than reported by others (38%) (3).

Nutritional requirements

Folic Acid

Enzyme-inducing AEDs and VPA interact with folic acid metabolism (15). Our local guidelines recommend that all women treated with enzyme-inducing AEDs supplement folic acid, but less than one third received this advice. We found folate deficiency in 11 (37%) of 30 women treated with enzyme-inducing AEDs who did not supplement ≥0.2 mg of folic acid, which is in agreement with findings from a controlled study (17).

Vitamin D and calcium

Some AEDs may alter bone mineral metabolism and compromise bone health, especially in women who have smaller bone mass (15). Our local guidelines include specific advice for women using hepatic enzyme–inducing AEDs, but awareness of this issue among neurologists and patients was not higher than that reported from a survey performed in 1995 (18).

Implementing good practice in epilepsy care

Our results, supporting those of others (13,14), strongly suggest that conventional strategies may not be sufficient to secure successful implementation of published guidelines. We hope that further research will identify interventions that more effectively alter professional behaviour (8). A weakness of guidelines for the care of WWE is that they are consensus based rather than evidence based and are not always consistent in their recommendations. Research is needed to improve the scientific base for future guidelines.

Conclusions

Case-note reviews revealed no clear evidence of change in clinical practice after an active attempt at implementing local guidelines for the care of WWE, although the follow-up during pregnancy seemed to have improved. Patients' knowledge of WWE issues compared favorably with that in published studies. Better strategies are needed to secure successful implementation of guidelines.

Acknowledgments

Acknowledgment:  We thank all the women with epilepsy who completed the questionnaire. The preparation of this article was supported by the Quality Improvement Foundation of the Norwegian Medical Association (grant 1019/2004).

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