Delivery outcome of women with epilepsy:a population-based cohort study

Authors

  • I Borthen,

    1.  Department of Clinical Medicine, University of Bergen, Norway
    2.  Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway
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  • MG Eide,

    1.  Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway
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  • AK Daltveit,

    1.  Department of Public Health and Primary Health Care, University of Bergen, Norway
    2.  Medical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway
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  • NE Gilhus

    1.  Department of Clinical Medicine, University of Bergen, Norway
    2.  Department of Neurology, Haukeland University Hospital, Bergen, Norway
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Dr I Borthen, Department of Gynaecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway.
Email ingrid.borthen@med.uib.no

Abstract

Please cite this paper as: Borthen I, Eide M, Daltveit A, Gilhus N. Delivery outcome of women with epilepsy: a population-based cohort study.
BJOG 2010;117:1537–1543.

Objective  To investigate whether women with epilepsy have increased risks of complications during labour, and to explore the impact of antiepileptic drug use.

Design  Population-based cohort study.

Setting  Data from the Medical Birth Registry of Norway 1999–2005.

Population  All births (n = 372 128) delivered in Norway, ensured through linkage with the National Population Registry run by Statistics Norway. All singleton births and the first child in multiple pregnancies were included, leaving 365 107 pregnancies for analysis.

Methods  Data from the Medical Birth Registry of Norway 1999–2005 were analysed.

Main outcome measures  Induction, caesarean section, use of forceps and vacuum, abnormal presentation, placental abruption, mechanical disproportion, postpartum haemorrhage, atony and Apgar score < 7 after 5 minutes.

Results  We compared 2805 pregnancies in women with a current or past history of epilepsy (0.8%) and 362 302 pregnancies in women without a history of epilepsy. Antiepileptic drugs were used in 33.6% (n = 942) of pregnant women with epilepsy. Women with epilepsy had an increased risk of induction [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.1–1.4], caesarean section (OR, 1.4; 95% CI, 1.3–1.6) and postpartum haemorrhage (OR, 1.2; 95% CI, 1.1–1.4) compared with women without epilepsy. These rates were even higher for women with epilepsy and antiepileptic drug use, with ORs (95% CIs) of 1.6 (1.4–1.9), 1.6 (1.4–1.9) and 1.5 (1.3–1.9), respectively. In addition, the risk of an Apgar score < 7 was higher (OR, 1.6; 95% CI, 1.1–2.4). For women with epilepsy without antiepileptic drug use, only a slightly increased risk of caesarean delivery was observed and no increased risk for any other complications studied.

Conclusions  Pregnant women with epilepsy have a low complication rate; however, they have a slightly increased risk of induction, caesarean section and postpartum haemorrhage. It is not possible to ascertain on the basis of this study whether this is a result of more severe epilepsy or antiepileptic drug use.

Introduction

Women with epilepsy have increased maternal risks compared with the general population.1 Pre-eclampsia, gestational hypertension and bleeding in pregnancy have been reported to be increased in women with epilepsy.2–5 The mechanisms underlying these risks are not fully understood, but seizures and the use of antiepileptic drugs (AEDs) seem to play a role.2,6 During labour, increased risks of induction,3,4,7,8 caesarean section (CS),3,5,7–10 and vacuum and forceps delivery3 have been found. However, recent studies have demonstrated no significant increase in obstetric interventions in this group.11,12 Whether this is a result of increased complications in pregnancy in women with epilepsy, the use of AEDs or the epilepsy itself is unclear. Bleeding in late pregnancy is reported to be a risk factor in women with epilepsy and the use of AEDs.2 Folate deficiency and alteration in the metabolism of vitamin K induced by AEDs have been postulated as a possible cause.13 Only a few studies have evaluated the effect of epilepsy on postpartum haemorrhage, and the results are conflicting. Four studies found no increased risk of postpartum haemorrhage or placental retention;6,7,9,11 in contrast, a recent study reported increased bleeding following vaginal delivery in women using AEDs.10 It is possible that AEDs may be a relevant factor, but it is not known whether these women have epilepsy or other chronic diseases. Other factors such as induction of labour, atony or lacerations in the birth canal may be relevant factors. Postpartum haemorrhage is the most important direct cause of maternal death, and comprises one-third of global maternal deaths.14 All women at risk of bleeding should therefore deliver in centres with facilities for blood transfusion,14 and it is important to assess the risk of haemorrhage in women with epilepsy. Obstetricians often lack relevant information for risk assessment, necessary for optimal clinical practice.

The aims of this study were to investigate whether women with epilepsy have an increased risk of complications, including haemorrhage, during labour and delivery, and to explore the impact of AED use in pregnancy.

Methods

The Medical Birth Registry of Norway (MBRN) is based on the compulsory notification of all births in Norway after 12 weeks of gestation, including abortions induced on medical indications.15 Complete ascertainment of births is ensured through linkage with the National Population Registry run by Statistics Norway. We used data on all births registered in MBRN in the period 1 December 1998–6 October 2005. Among the 372 128 registered births, all singleton births and the first child in multiple pregnancies were included, leaving 365 107 births for analysis. Miscarriages and stillbirths below week 21 were also included, but women using AEDs without having a diagnosis of epilepsy were excluded (n = 133). The study population was divided into births in women who gave a past or present history of epilepsy (henceforth designated as ‘women with epilepsy’), n = 2805 (0.8%), and those who did not, n = 362 169 (reference group).

In Norway, more than 99% of pregnant women receive antenatal care, mainly provided by general practitioners.16 A standardised antenatal form is filled in for each pregnancy, starting at the first antenatal visit, and brought to the obstetric unit at delivery. These data are transferred to the MBRN notification form by the midwives attending the delivery.15 Furthermore, all data related to the delivery are recorded by the midwife or doctor, and follow-up data are added until discharge.15 An unchanged MBRN notification form was used in the study period. The maternal epilepsy diagnosis is notified in a checkbox on the notification form, or by a code according to the International Classification of Diseases, 10th revision (ICD-10), based on textual information on the notification form. Data on maternal education were obtained from Statistics Norway. Data on all other variables were obtained from MBRN.

Medication is notified in MBRN according to the Anatomical Therapeutic Chemical (ATC) Classification System, consisting of a five-digit ATC number. Pregnancies registered with an anticonvulsant drug were categorised as exposed to AEDs. The AEDs were mainly used as monotherapy (86%).17

The MBRN requests dichotomous data (yes/no) on both procedures and complications during labour and delivery with detailed information in free text.18 In this study, the outcomes of interest were as follows: induction of labour (yes/no), abruption of placenta (yes/no), abnormal presentation (breech, oblique, transverse), operative vaginal delivery (including vaginal breech delivery, forceps and vacuum delivery), intrauterine asphyxia (yes/no), prolonged labour during second stage (yes/no), attenuation of contractions and use of stimulation (yes/no), mechanical disproportion (yes/no), placenta or amniotic disturbances (yes/no), atony after delivery (yes/no) and CS (acute or planned). Whether or not CS was planned before delivery was recorded. Deliveries planned as CS, but performed as emergency procedures, were assigned to the ‘acute CS’ group. Postpartum haemorrhage, defined as bleeding during labour and delivery and 24 hours postpartum, is notified if ≥ 500 ml, and with separate checkboxes for 500–1500 ml and > 1500 ml. Pre-eclampsia and late vaginal bleeding are notified by checkboxes and have been defined in a previous study.2

The MBRN form explicitly requests numerical data for birth weight, gestational age and Apgar score. Gestational age was calculated from the ultrasonographic measurements performed at 18–19 weeks of gestation. When unavailable, gestational age was estimated on the basis of the first day of the last menstrual period. Gestational age was categorised as < 34 weeks, 34–36 weeks and ≥ 37 weeks. Pregnancies ≥ 294 days of gestation (> 42 weeks) were defined as post-term.

Supplementation of folic acid and multivitamins (four times per week or more) prior to pregnancy and during pregnancy was notified by checkboxes (yes/no).

Statistical analysis

Crude and adjusted odds ratio (ORs) with 95% confidence intervals (CIs) were calculated by multiple logistic regression in SPSS 15.0 for Windows (SPSS Inc., Chicago, IL, USA). Potential confounding variables analysed as categorical variables in the multivariable regression models included maternal age at delivery (< 24, 25–29, 30–34, ≥ 35 years), smoking during pregnancy (yes/no), highest attained maternal educational level (0–9, 10–14, ≥ 15 years) and diabetes. Diabetes was either gestational diabetes (yes/no) or diabetes type 1 or 2 (yes/no). As women with diabetes have no increased risk of haemorrhage or atony, diabetes was not included in the analysis of bleeding and atony after delivery. Folic acid supplement (yes/no) and gestational age (< 34 weeks, 34–36 weeks, ≥ 37 weeks) were evaluated as potential confounders during the analysis. Cross-tabulated measures for small samples with an expected cell count of < 5 were analysed by Fisher’s exact test and presented as unadjusted P values with corresponding ORs. Two-sided P values of < 0.05 were considered to be statistically significant. Interactions were evaluated in stratified analysis (para 0 and para 1+, gestational age < 37 weeks and ≥ 37 weeks) and with interaction terms in logistic models.

Research on anonymous registry data is routinely exempt from ethical review and informed consent requirements by the ethics research committees in Norway. This study was considered to be exempt by The Norwegian Institute of Public Health institutional review board.

Results

In our study population, 2805 births (0.8%) occurred in women with epilepsy. Women with past or present epilepsy had a lower education level than the reference group, were younger and were more often nulliparous (Table 1). Of the women with epilepsy, 33.6% (n = 942) were exposed to AEDs. The most commonly used AEDs were carbamazepine [41.2% (n = 388) used this medication as monotherapy], lamotrigine [used by 24.7% (n = 233)] and valproate [used as monotherapy by 22.8% (n = 215)]. Polytherapy was used in 11.1% (n = 105) and valproate was used in combination with other AEDs in 40 women with epilepsy. The mean birth weights (±standard deviation) were 3464 ± 723 g in the epilepsy group, 3435 ± 770 g in the epilepsy group with AED use and 3520 ± 668 g in the reference group, a difference of 56 g (P < 0.001) and 85 g (P < 0.001), respectively.

Table 1.   Characteristics of the study population, Medical Birth Registry of Norway 1999–2005
Maternal characteristicEpilepsy, all (n = 2805)Epilepsy without AEDs (n = 1863)Epilepsy with AEDs (n = 942)No epilepsy (reference) (n = 362 302)
  1. *Mean and standard deviations (SDs) given for maternal age, length of pregnancy and weight of baby by independent samples t-tests.

  2. **P < 0.001.

  3. ***P < 0.05.

  4. ****P < 0.01.

Education ≥ 15 years, % (n)27.0 (757)**28.1 (524)**24.7 (233)**34.6 (125 187)
Smoking, % (n)24.4 (685)**23.9 (445)**25.5 (240)**19.0 (68 728)
Nulliparous, % (n)42.2 (1185)41.7 (776)43.4 (409)40.7 (147 310)
Multiple pregnancies, % (n)4.0 (114)3.8 (73)4.3 (41)3.9 (14 270)
Diabetes, type 1 and 2, % (n)1.1 (32)**1.3 (25)**0.7 (7)0.6 (2197)
Preconception folate use, % (n)18.8 (526)**12.2 (228)**31.6 (298)**9.6 (34 794)
Folate use in pregnancy, % (n)43.6 (1223)**32.3 (601)**66 (622)**28.5 (103 380)
Age in years, mean (SD)*28.8 (5.2)**28.8 (5.2)**28.9 (5.2)***29.3 (5.0)
Length of pregnancy in days (SD)*275 (19.4)**276 (18.7)***274 (20.6)**277 (17.2)
Weight of baby in grams (SD)*3464 (723)**3479 (698)****3435 (770)**3520 (668)

Among women with epilepsy, 4.0% delivered before week 34, compared with 3.2% in the reference group (OR, 1.2; 95% CI, 1.0–1.5). For women with epilepsy and AED use, this rate was 4.9% (OR, 1.6; 95% CI, 1.2–2.1).

Women with epilepsy more often had an induction of labour: 15.8% compared with 12.9% in the reference group (OR, 1.3; 95% CI, 1.1–1.4) (Table 2). We did not observe any differences in the proportions of post-term pregnancies, pre-eclampsia or bleeding late in pregnancy in women with epilepsy relative to women without epilepsy among the induced births.

Table 2.   Delivery outcomes in women with epilepsy compared with all women with no epilepsy, Medical Birth Registry of Norway 1999–2005
Delivery outcomeNo epilepsy% (n)Epilepsy, allEpilepsy, no AED useEpilepsy, AED use
 % (n)Crude OR (95% CI)Adjusted* OR (95% CI)% (n)Adjusted* OR (95% CI)% (n)Adjusted* OR (95% CI)
  1. AED, antiepileptic drug; CI, confidence interval, OR, odds ratio.

  2. *Adjusted for the following categorised factors: maternal age (years), < 20, 20–34, ≥ 35; maternal education (years), < 11, 11–14, ≥ 15; parity, 0, 1+; smoking, no/yes; diabetes, no/yes (except for postpartum atony and haemorrhage, where diabetes is excluded).

Induction12.9 (46 627)15.8 (443)1.3 (1.1–1.4)1.3 (1.1–1.4)13.9 (259)1.1 (0.9–1.2)19.5 (184)1.6 (1.4–1.9)
Caesarean
All14.3 (51 806)19.1 (536)1.4 (1.3–1.6)1.4 (1.3–1.6)18.1 (337)1.3 (1.2–1.5)21.1 (199)1.6 (1.4–1.9)
Acute8.6 (31 077)10.3 (288)1.2 (1.1–1.4)1.2 (1.1–1.4)9.7 (181)1.1 (1.0–1.3)11.4 (107)1.3 (1.1–1.6)
Planned4.6 (16 507)7.4 (207)1.7 (1.4–1.9)1.7 (1.5–2.0)6.9 (129)1.5 (1.3–1.9)8.3 (78)1.9 (1.5–2.4)
Cephalic vaginal
Forceps1.3 (4 692)1.4 (38)1.0 (0.8–1.4)1.0 (0.7–1.4)1.1 (21)0.9 (0.6–1.3)1.8 (17)1.3 (0.9–2.2)
Vacuum6.6 (23 854)7.5 (211)1.2 (1.0–1.3)1.2 (1.0–1.3)7.2 (134)1.1 (0.9–1.3)8.2 (77)1.2 (1.0–1.6)
Postpartum
Atony4.1 (14 835)4.9 (138)1.2 (1.0–1.4)1.2 (1.0–1.5)4.6 (85)1.1 (0.9–1.4)5.6 (53)1.4 (1.1–1.9)
Haemorrhage ≥ 500 ml13.6 (49 252)16.2 (454)1.2 (1.1–1.4)1.2 (1.1–1.4)14.8 (276)1.1 (1.0–1.3)18.9 (178)1.5 (1.3–1.8)
Apgar < 7 after 5 minutes1.7 (6 022)1.9 (54)1.2 (0.9–1.5)1.2 (0.9–1.6)1.6 (30)1.0 (0.7–1.4)2.6 (24)1.6 (1.1–2.4)

Women with epilepsy were delivered by CS more often than women in the reference group (OR, 1.4; 95% CI, 1.3–1.6). As induction often ended in CS, we excluded all women with induction in the analysis of CS; however, the results remained almost unchanged.

Women with epilepsy had more postpartum haemorrhage than the general population (OR, 1.2; 95% CI, 1.1–1.4), although no increased risk of excessive bleeding (i.e. > 1500 ml) was observed. Accounting for mode of delivery, 11.1% of women with epilepsy and a vaginal delivery had a postpartum haemorrhage, compared with 9.4% of women without epilepsy (OR, 1.2; 95% CI, 1.1–1.4). In vaginal operative deliveries, the rate was even higher: 25.9% versus 20.2% (OR, 1.4; 95% CI, 1.1–1.8); however, the risk after CS was similar to that in the reference group (OR, 0.9; 95% CI, 0.8–1.1). Women with epilepsy and an operative vaginal delivery had a higher risk of uterine atony (OR, 1.7; 95% CI, 1.1–2.5). The risks of abruption of placenta, abnormal presentations, attenuation of contractions, prolonged second stage, mechanical disproportion, operative vaginal delivery, placenta and amniotic disturbances, and intrauterine death were not increased in women with epilepsy compared with the reference group.

Among women with epilepsy not using AEDs, no increased risks were observed for the induction of labour or postpartum haemorrhage (Table 2). However, we observed an increased risk of being delivered by CS (OR, 1.3; 95% CI, 1.2–1.5).

The risks of both induction and CS were increased significantly in women with epilepsy using AEDs relative to the reference group without epilepsy (OR, 1.6; 95% CI, 1.4–1.9). Women using lamotrigine monotherapy had the highest risk of being induced [24.3% (n = 57); OR, 2.2; 95% CI, 1.6–2.9), and women using polytherapy and valproate as monotherapy had the highest risks of having CS (OR, 2.4; 95% CI, 1.6–3.7; and OR, 1.7; 95% CI, 1.2–2.4, respectively) (Table 3). Women using AEDs also had an increased risk of postpartum haemorrhage (OR, 1.5; 95% CI, 1.3–1.8), and women using valproate as monotherapy had the highest risk [24.4% (n = 43); OR, 2.1; 95% CI, 1.5–3.0). Corresponding risks for women using lamotrigine and carbamazepine were 20.4% (n = 48) and 16.8% (n = 66), respectively, versus 13.6% of the reference group (OR, 1.6; 95% CI, 1.2–2.2; and OR, 1.3; 95% CI, 1.0–1.7, respectively). In vaginal deliveries, 12.9% of women with epilepsy and AED use had a haemorrhage compared with 9.4% in the reference group (OR, 1.4; 95% CI, 1.1–1.8), and, in operative vaginal deliveries, the risk was even greater (OR, 1.8; 95% CI, 1.2–2.7). There was an increased risk for neonates exposed to AEDs to have an Apgar score < 7 after 5 minutes (OR, 1.6; 95% CI, 1.1–2.4).

Table 3.   Delivery outcomes in women with epilepsy and antiepileptic drug (AED) use compared with all women with no epilepsy, Medical Birth Registry of Norway 1999–2005
Delivery outcomeNo epilepsy% (n)Polytherapy (n = 105)Valproate (n = 215)Carbamazepine (n = 388)Lamotrigine (n = 233)
 % (n)Adjusted OR (95% CI)% (n)Adjusted OR (95% CI)% (n)Adjusted OR (95% CI)% (n)Adjusted OR (95% CI)
  1. AED, antiepileptic drug; CI, confidence interval, OR, odds ratio.

  2. †Adjusted for the following categorised factors: maternal age (years), < 20, 20–34, ‡ 35; maternal education (years), < 11, 11–14, ‡ 15; parity, 0, 1+; smoking, no/yes; diabetes, no/yes (except for postpartum atony and haemorrhage, where diabetes is excluded).

Induction12.9 (46 627)22.9 (24)1.9 (1.2–3.1)23.3 (41)2.1 (1.5–3.0)14.5 (57)1.1 (0.8–1.5)24.3 (57)2.2 (1.6–2.9)
Caesarean
All14.3 (51 806)29.5 (31)2.4 (1.6–3.7)21.0 (37)1.7 (1.2–2.4)20.7 (81)1.5 (1.2–1.9)18.7 (44)1.4 (1.0–1.9)
Acute8.6 (31 077)14.3 (15)1.6 (0.9–2.8)13.6 (24)1.7 (1.1–2.7)10.7 (42)1.2 (0.9–1.7)11.1 (26)1.3 (0.8–1.9)
Planned4.6 (16 507)14.3 (15)3.6 (2.1–6.3)8.4 (13)1.9 (1.0–3.2)7.7 (30)1.7 (1.1–2.4)6.8 (16)1.7 (1.0–2.9)
Cephalic vaginal
All operative8.9 (32 085)12.4 (13)1.3 (0.7–2.4)11.9 (21)1.4 (0.9–2.2)9.9 (39)1.1 (0.8–1.6)12.8 (30)1.4 (0.9–2.0)
Postpartum
Atony4.1 (14 835)7.6 (8)1.9 (0.9–3.9)6.8 (12)1.8 (1.0–3.2)5.4 (21)1.3 (0.9–2.1)5.1 (12)1.2 (0.7–2.2)
Haemorrhage ≥ 50 ml13.6 (49 252)16.2 (17)1.2 (0.7–2.0)24.4 (43)2.1 (1.5–3.0)16.8 (66)1.3 (1.0–1.7)20.4 (48)1.6 (1.2–2.2)
Apgar < 7 after 5 minutes1.7 (6 022)2.9 (3)1.7 (0.6–5.5)1.7 (3)1.0 (0.3–3.2)2.8 (11)1.7 (0.9–3.1)3.0 (7)1.9 (0.9–4.0)

When comparing women with epilepsy with and without AED use, we observed, for those with AED use, a borderline increased risk of CS (OR, 1.2; 95% CI, 1.0–1.5), an increased risk of induction (OR, 1.5; 95% CI, 1.2–1.9), haemorrhage (OR, 1.4; 95% CI, 1.1–1.7) and Apgar score < 7 after 5 minutes (OR, 1.7; 95% CI, 1.0–3.0).

No significant interactions between parity or gestational age and epilepsy were found with respect to the occurrence of induction, CS and haemorrhage.

As crude and adjusted measures were similar, only the adjusted values are reported in the text. Excluding multiple pregnancies (4.0% in women with epilepsy and 3.9% in the reference group) and miscarriages and abortions below 21 weeks of gestation (0.5% in women with epilepsy and 0.3% in the reference group) did not influence the results (data not shown). Folic acid use and gestational age were evaluated as potential confounders and had no impact on any of the results above.

Discussion

Principal findings and interpretation

This study demonstrates that the majority of women with a past or present history of epilepsy had a satisfactory course of labour. Nevertheless, women with epilepsy using AEDs had a 1.6-fold increased risk of induction compared with the general obstetric population, a nearly two-fold increased risk of being delivered by a planned CS and a 1.5-fold increased risk of postpartum haemorrhage. Women with epilepsy without AED use had a 1.5-fold increased risk of being delivered by a planned CS, but no increased risk of induction or bleeding.

Our historical cohort data are based on mandatory reporting in a population-based registry over a 6-year period, thus comprising all cases of epilepsy in Norway (population of 4.7 million) who gave birth in this period. This excludes the possibility of selection bias. The large study size provides high precision, and the standardised collection of data provides high validity in the estimates of effect. Reported maternal epilepsy in 0.8% of pregnancies indicates high diagnostic sensitivity, the prevalence in other epidemiological studies being 0.5–0.7%.4,9,12 Earlier reports on MBRN data have demonstrated high diagnostic validity regarding maternal disease and outcome.19,20 As a large proportion of the epilepsy group was untreated, potential under-reporting of AED treatment is a concern, and any misclassification could lead to bias in estimating the risks of women with epilepsy and AED use. However, a recent study from Norway confirms our findings of AED use in 0.3% of women during pregnancy.21 The large proportion of untreated epilepsy includes women in whom AED use is not regarded as necessary during pregnancy, and women with a past history of epilepsy; also some women with more severe epilepsy may avoid pregnancy. Patients on AEDs may differ from untreated patients according to the type or aetiology of epilepsy or seizure characteristics. In MBRN, neither the type nor status of epilepsy is notified.

The induction rate in women with epilepsy was increased and greatest in those using AEDs. This is in accordance with two previous studies in which 33% and 19% were induced,4,7 but contrary to the finding in a study from Japan where no difference was seen.22 According to guidelines in Norway23 and England,24 epilepsy is not an indication for induction in uncomplicated pregnancies. Recently, we have found that women with epilepsy more often have mild pre-eclampsia,2 but this could not explain the increased induction rate in the present study. The EURAP register found that 58.3% of women with epilepsy had no seizures during pregnancy, 15.9% had a decrease in seizures and 17.3% had an increase in seizures.25 One might speculate that those with high seizure activity more often have inductions, but this could not be investigated in our study. The finding of no increased complication rates in induced women within the epilepsy group makes it likely that the diagnosis of epilepsy was the main reason for induction. Unfortunately, MBRN gives no exact information about the indications for induction.

The rate of CS in women with epilepsy was markedly increased in contrast with three recent studies.4,11,12 These studies reported risks in a hospital-based population, whereas the present study examines the CS rate in an unselected and complete epilepsy cohort. Recent population-based cohort studies from Israel and Sweden, investigating pregnant women using AEDs, also reported increased intervention rates.7,10 Most chronic disorders increase the likelihood of CS.26 Epilepsy represents a significant disorder, but is not an indication for CS unless either a seizure occurs during the second stage of labour or the patient cannot cooperate during a vaginal delivery.13 The risk of seizures increases around the time of delivery.27 However, less than 2% of women with epilepsy experience a seizure during labour.28 Uncertainty, together with the misperception of an increased risk of complications, may account for the high rates.7 We could not identify any complications during pregnancy and labour which could account for the increased planned caesarean rate, although there was no information in MBRN on the type of epilepsy or the occurrence of epileptic seizures during labour.

Postpartum haemorrhage was more common in women with epilepsy using AEDs, in line with a previous study.10 AEDs may be a relevant causal factor, as women with epilepsy without AED use showed no increased risk of bleeding. In addition, late vaginal bleeding in pregnancy is more common in women with epilepsy using AEDs.2 AED-induced folate deficiency and alteration in the metabolism of vitamin K-dependent blood clotting factors have been suggested as possible causes of vaginal bleeding in late pregnancy.13 The increased bleeding after delivery may be caused by the same mechanism. However, the use, or not, of folic acid did not influence our results. Vitamin K prophylaxis is recommended in the last month of pregnancy in Norway,23 but a recent study has debated the use of vitamin K in late pregnancy for women taking enzyme-inducing AEDs.29 The UK National Institute for Health and Clinical Excellence (NICE) guidelines and the American Academy of Neurology (AAN) Quality Standards Subcommittee no longer recommend vitamin K to women in pregnancy, only to neonates at delivery.24,30 In addition, these women had an increased risk of uterine atony, and this was probably a contributing factor for excessive bleeding. Other risk factors for postpartum haemorrhage are induction and prolonged labour, but these were not observed in the present study.

Conclusions and implications for clinicians

Our study of a large complete cohort of women with epilepsy has demonstrated few complications during labour. Women with epilepsy not using AEDs have no increased risk of induction or haemorrhage, but an increased risk of being delivered by CS. In contrast, women with epilepsy and AED use have a slightly increased risk of induction, CS and postpartum haemorrhage. It is not possible to ascertain, on the basis of this study, whether this is caused by more severe epilepsy or AED use. Special attention should be paid to women with epilepsy using AEDs and having a vaginal delivery, as the risk of bleeding is increased. This might be prevented by appropriate training of the obstetric team. Future studies evaluating the use of folate and vitamin K in mothers with epilepsy and AED use should focus on mothers bleeding late in pregnancy and postpartum. The type of epilepsy and seizure frequency in pregnancy and labour need to be documented and the reasons for the increased rate of interventions need to be identified to lower the induction rate and CS.

Disclosure of interests

There were no conflicts of interest.

Contribution to authorship

IB conceived and designed the study, analysed and interpreted the data and drafted the article. She is the guarantor. MGE designed the study, interpreted the data and revised the article. AKD and NEG conceived and designed the study, interpreted the data and revised the article. All authors approved the final version.

Details of ethics approval

Research on anonymous registry data is routinely exempt from ethical review and informed consent requirements by the ethics research committees in Norway. This study was considered to be exempt by The Norwegian Institute of Public Health institutional review board.

Funding

This study was supported by the Norwegian Research Council through the NevroNor research programme.

Acknowledgement

None.

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