Epilepsy and eating disorders during pregnancy: Prevalence, complications and birth outcome

Open ArchivePublished:February 21, 2015DOI:https://doi.org/10.1016/j.seizure.2015.02.014

      Highlights

      • Women with epilepsy have more binge eating disorder.
      • Women using antiepileptic drugs have more binge eating disorder during pregnancy.
      • Epilepsy and eating disorders increase risk of complications during pregnancy.
      • We used data from The Norwegian Mother and Child Cohort Study.

      Abstract

      Purpose

      The aim was to investigate the prevalence of eating disorders and its relation to pregnancy and delivery complications in childbearing women with epilepsy (WWE).

      Method

      This study is based on The Norwegian Mother and Child Cohort Study (MoBa) linked to the Medical Birth Registry of Norway. Epilepsy was reported in 706 pregnancies. The remaining cohort (n = 106,511) served as the reference group. Eating disorders were diagnosed using DSM-IV criteria adjusted for pregnancy. The risk of preeclampsia, gestational hypertension, diabetes and weight gain during pregnancy as well as delivery outcome (small for gestational age, large for gestational age, ponderal index, low APGAR score, small head circumference) were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for maternal age, smoking, parity and socioeconomic factors.

      Results

      Pregnant WWE were significantly more likely to have binge eating disorder (6.5% vs. 4.7%, p < 0.05). WWE and comorbid eating disorders had significantly more preeclampsia (7.9% vs. 3.7%, p < 0.05), peripartum depression and/or anxiety (40.4% vs. 17.8%, p < 0.001) and operative delivery (38.2% vs. 23.5%, p < 0.001) than the reference group without epilepsy or eating disorders. After adjustment for confounders, a significantly increased risk of operative delivery (OR 1.96, CI 1.26–3.05) and peripartum depression and/or anxiety (OR 2.17, CI 1.40–3.36) was demonstrated.

      Conclusion

      Eating disorders in WWE contribute to the increased risk of pregnancy and delivery complications. Health personnel should be aware of eating disorders in WWE and refer them for treatment before pregnancy.

      Keywords

      1. Introduction

      Antiepileptic drug (AED) treatment is used by 0.2–0.7% of pregnant women [
      • Wide K.
      • Winbladh B.
      • Kallen B.
      Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation-wide, population-based register study.
      ,
      • Malm H.
      • Martikainen J.
      • Klaukka T.
      • Neuvonen P.J.
      Prescription drugs during pregnancy and lactation – a Finnish register-based study.
      ]. Several obstetrical complications such as preeclampsia, gestational hypertension, caesarian delivery, congenital malformations and low birth weight occur more frequently in these women than in women without epilepsy [
      • Borthen I.
      • Eide M.G.
      • Veiby G.
      • Daltveit A.K.
      • Gilhus N.E.
      Complications during pregnancy in women with epilepsy: population-based cohort study.
      ]. Adverse birth outcomes in women with epilepsy (WWE) are believed to be mediated by AED use, although the exact mechanisms of action and the role of confounding factors remain unclear. Comorbid eating disorders (ED) are an unexplored potential contributor to pregnancy complications in WWE.
      Using data from The Norwegian Mother and Child Cohort Study (MoBa), Reiter et al. [
      • Reiter S.F.
      • Veiby G.
      • Daltveit A.K.
      • Engelsen B.A.
      • Gilhus N.E.
      Psychiatric comorbidity and social aspects in pregnant women with epilepsy – the Norwegian Mother and Child Cohort Study.
      ] found an increased life time prevalence of self-reported, unspecified ED in pregnant WWE. Rai et al. also found an increased frequency of ED (OR 2.9) in non-pregnant persons with epilepsy [
      • Rai D.
      • Kerr M.P.
      • McManus S.
      • Jordanova V.
      • Lewis G.
      • Brugha T.S.
      Epilepsy and psychiatric comorbidity: a nationally representative population-based study.
      ].
      Adverse pregnancy outcomes are more frequent in women with ED, especially for the subgroup with binge eating disorder (BED) [
      • Bulik C.M.
      • Von Holle A.
      • Siega-Riz A.M.
      • Torgersen L.
      • Lie K.K.
      • Hamer R.M.
      • et al.
      Birth outcomes in women with eating disorders in the Norwegian Mother and Child Cohort Study (MoBa).
      ]. Women with BED deliver babies that are large for gestational age and have an increased risk of caesarian section. An increased rate of miscarriages has been noted in both anorexia nervosa (AN) and bulimia nervosa (BN) [
      • Bulik C.M.
      • Sullivan P.F.
      • Fear J.L.
      • Pickering A.
      • Dawn A.
      • McCullin M.
      Fertility and reproduction in women with anorexia nervosa: a controlled study.
      ,
      • Keel P.K.
      • Dorer D.J.
      • Eddy K.T.
      • Franko D.
      • Charatan D.L.
      • Herzog D.B.
      Predictors of mortality in eating disorders.
      ]. ED have also been linked to an increased risk of stillbirth, low birth weight, low Apgar scores, breech presentation, lower weight-for-length offspring trajectories and cleft lip and palate [
      • Stewart D.E.
      • Raskin J.
      • Garfinkel P.E.
      • MacDonald O.L.
      • Robinson G.E.
      Anorexia nervosa: bulimia, and pregnancy.
      ,
      • Bulik C.M.
      • Von Holle A.
      • Siega-Riz A.M.
      • Torgersen L.
      • Lie K.K.
      • Hamer R.M.
      • et al.
      Birth outcomes in women with eating disorders in the Norwegian Mother and Child Cohort Study (MoBa).
      ,
      • Perrin E.M.
      • Von-Holle A.
      • Zerwas S.
      • Skinner A.C.
      • Reba-Harrison L.
      • Hamer R.M.
      • et al.
      Weight-for-length trajectories in the first year of life in children of mothers with eating disorders in a large Norwegian cohort.
      ].
      As both epilepsy and ED increase the risk of complications during pregnancy and delivery, we investigated the prevalence and subtypes of this combination during pregnancy, and estimated possible impacts of ED in epilepsy on pregnancy and birth outcome in WWE.

      2. Materials and methods

      The Norwegian Mother and Child Cohort Study (MoBa) is a prospective population-based pregnancy cohort study conducted by the Norwegian Institute of Public Health. Participants were recruited from all over Norway from 1999 to 2008. The women consented to participation in 40.6% of the pregnancies. The cohort now includes 114,500 children, 95,200 mothers and 75,200 fathers. The response rate was 45% [
      • Magnus P.
      • Irgens L.M.
      • Haug K.
      • Nystad W.
      • Skjaerven R.
      • Stoltenberg C.
      Cohort profile: the Norwegian Mother and Child Cohort Study.
      ]. The women received standardized questionnaires addressing information on maternal epilepsy, psychiatric symptoms and socioeconomic status. The MoBa database is linked to the Medical Birth Registry of Norway that contains information on pregnancy and delivery complications.
      The MoBa database comprises 706 pregnancies in women with epilepsy and 106,508 pregnancies in women without epilepsy. Information concerning ED was available for 73,171 pregnancies. The MoBa epilepsy cohort has been validated [
      • Veiby G.
      • Daltveit A.K.
      • Schjølberg S.
      • Stoltenberg C.
      • Øyen A.S.
      • Vollset S.E.
      • et al.
      Exposure to antiepileptic drugs in utero and child development: a prospective population-based study.
      ,
      • Bjørk M.B.
      • Veiby G.
      • Spigset O.
      • Gilhus N.E.
      Using the Norwegian Mother and Child Cohort Study to determine risk factors for delayed development and neuropsychiatric symptoms in the offspring of parents with epilepsy.
      ].
      The women answered questions in accordance with DSM-IV criteria for AN, BN and BED. The questions were slightly adjusted due to the cohort being pregnant, amenorrhea was not required in AN. We also evaluated “impaired bodyimage” defined as fulfilling the AN criteria, except for amenorrhea and low BMI criteria. The frequency of fasting, use of laxantia and vomiting during pregnancy was investigated. The rates of ED in the women without epilepsy in the MoBa study have been validated [
      • Watson H.J.
      • Von Holle A.
      • Hamer R.M.
      • Konph Berg C.
      • Torgersen L.
      • Magnus P.
      • et al.
      Remission, continuation and incidence of eating disorders during early pregnancy: a validation study in a population-based birth cohort.
      ].
      We investigated the relationship between epilepsy and any type of ED (except for impaired body image) and hypertension during pregnancy, diabetes during pregnancy, preeclampsia, peripartum depression and/or anxiety [
      • Bjørk M.B.
      • Veiby G.
      • Reiter S.F.
      • Berle J.Ø.
      • Daltveit A.K.
      • Spigset O.
      • et al.
      Depression and anxiety in women with epilepsy during pregnancy and after delivery: a prospective population-based cohort study on frequency, risk factors, medication and prognosis.
      ], excessive pregnancy weight gain (>16 kg), operative deliveries (caesarian section, use of vacuum or forceps), small for gestational age (<10th percentile), large for gestational age (>10th percentile), small head circumference (<10th percentile) [
      • Skjaerven R.
      • Gjessing H.K.
      • Bakketeig L.S.
      Birthweight by gestational age in Norway.
      ], low Apgar score (<7 after 5 min) and ponderal index (weight/length3, <10th percentile and >90th percentile). Neonatologists have preferentially used the ponderal index rather than small for gestational age as an indicator of nutritional status in the child, and the variable is a predictor of neonatal disease [
      • Bettiol H.
      Neonatal anthropometry and neonatal outcome.
      ].
      IBM SPSS Statistics version 21 was used. We investigated group differences using Student's t test and Pearson's χ2 test (Fisher's exact test if any cross table cell had an expected count < 5). Binary logistic regression was used to estimate the odds ratio (OR) with 95% confidence interval (CI) for pregnancy and delivery complications adjusted for the confounding factors maternal age, parity, smoking and socioeconomic factors (low household income, low education or being a single mother).
      The study was approved by the Regional Ethical Committee in Western Norway.

      3. Results

      WWE in the MoBa cohort more frequently had lower educational attainment, low income, single parenting, and were younger than women without epilepsy [
      • Bjørk M.B.
      • Veiby G.
      • Reiter S.F.
      • Berle J.Ø.
      • Daltveit A.K.
      • Spigset O.
      • et al.
      Depression and anxiety in women with epilepsy during pregnancy and after delivery: a prospective population-based cohort study on frequency, risk factors, medication and prognosis.
      ]. They also had significantly higher weight and BMI than the reference group (Table 1).
      Table 1Weight, BMI and eating disorders in women with and without epilepsy.
      Reference

      n = 106,508
      Epilepsy

      n = 706
      No AED
      AED=antiepileptic drugs.


      n = 367
      AED

      n = 338
      Weight (SD)68.0 (12.9)69.5 (13.7)**69.2 (13.0)*69.7 (14.3)*
      BMI (SD)24.0 (4.3)24.7 (4.6)***24.6 (4.5)24.8 (4.8)
      Impaired bodyimage
      Impaired bodyimage=DSM-IV criteria for anorexia nervosa, but amenorrhea and BMI<18.5 were not required.
      2356 (3.6%)30 (6.1%)**13 (4.9%)17 (7.5%)**
      BED
      BED=binge eating disorder.
      pre-pregnancy
      Pre-pregnancy=last 6 months before pregnancy.
      3165 (3.3%)30 (4.5%)13 (3.7%)17 (5.3%)*
      BED during pregnancy
      During pregnancy=gestation week 17–19.
      4298 (4.7%)41 (6.5%)*21 (6.3%)20 (6.6%)
      Bulimia pre-pregnancy
      Pre-pregnancy=last 6 months before pregnancy.
      1747 (1.7%)7 (1.0%)4 (1.1%)3 (0.9%)
      Bulimia during pregnancy
      During pregnancy=gestation week 17–19.
      466 (0.5%)1 (0.1%)1 (0.3%)0 (0%)
      Use of laxantia during pregnancy
      During pregnancy=gestation week 17–19.
      ,
      Use of laxantia, fasting or vomiting at least once a week with the purpose of controlling body weight. *p<0.05; **p<0.01; ***p<0.001 vs. the reference group.
      79 (0.1%)000
      Fasting during pregnancy
      During pregnancy=gestation week 17–19.
      ,
      Use of laxantia, fasting or vomiting at least once a week with the purpose of controlling body weight. *p<0.05; **p<0.01; ***p<0.001 vs. the reference group.
      60 (0.1%)2 (0.3%)*1 (0.3%)1 (0.3%)
      Vomiting during pregnancy
      During pregnancy=gestation week 17–19.
      ,
      Use of laxantia, fasting or vomiting at least once a week with the purpose of controlling body weight. *p<0.05; **p<0.01; ***p<0.001 vs. the reference group.
      392 (0.4%)4 (0.7%)2 (0.7%)2 (0.6%)
      a BED = binge eating disorder.
      b AED = antiepileptic drugs.
      c Pre-pregnancy = last 6 months before pregnancy.
      d During pregnancy = gestation week 17–19.
      e Impaired bodyimage = DSM-IV criteria for anorexia nervosa, but amenorrhea and BMI < 18.5 were not required.
      f Use of laxantia, fasting or vomiting at least once a week with the purpose of controlling body weight.*p < 0.05; **p < 0.01; ***p < 0.001 vs. the reference group.
      There was a significantly increased rate of BED and “impaired body image” during pregnancy in WWE compared to women without epilepsy (Table 1). “Impaired body image” was significantly increased in both women using AED monotherapy (6.9%, p < 0.05, n = 266) and polytherapy (9.4%, p < 0.05, n = 72), as compared with the reference group (3.6%). No difference in prevalence was found for bulimia or anorexia before or during pregnancy.
      WWE and comorbid ED had significantly more often preeclampsia (7.9% vs. 3.7%), peripartum depression and/or anxiety (40.4% vs. 17.8%) and operative delivery (38.2% vs. 23.5%) than women without epilepsy and no ED (Fig. 1). WWE and comorbid ED had more peripartum depression and/or anxiety than WWE without ED (40.4% vs. 24.2%, p < 0.01). No confounding factors were considered in this analysis.
      Figure thumbnail gr1
      Fig. 1Pregnancy and delivery complications (plot A) and birth outcome (plot B) according to a diagnosis of epilepsy and/or eating disorders. Significance levels are marked with *, compared with the reference group without eating disorder. W = with, wo = without.
      After adjusting for confounding factors, WWE and comorbid ED had a significantly greater risk of peripartum depression and/or anxiety (OR = 2.17, CI 1.4–3.4, p < 0.001) and operative delivery (OR = 1.96, CI 1.3–3.0, p < 0.01, Fig. 2). After additional adjustment for AED use, the risk of operative delivery was no longer significantly higher (OR 1.35, CI 0.7–2.5, p < 0.35).
      Figure thumbnail gr2
      Fig. 2Complications during pregnancy, delivery and birth outcome. WWE and ED (grey markers) and WWE and no ED (black markers) compared with the reference group (all other women in MoBa). Risk of complications during pregnancy (plot A) and risk of adverse birth outcome (plot B). The estimates are adjusted for parity, maternal age, smoking and socioeconomic factors. Depression/anx = peripartum depression and/or anxiety. Op. delivery = caesarian section, use of vacuum or forceps. PI = ponderal index. SGA/LGA = small/large for gestational age. SGA head = small for gestational age head circumference. Low Apgar: <7 after 5 min.

      4. Discussion

      Pregnant WWE have an increased risk of binge eating disorder. WWE and comorbid ED more often had operative deliveries and pregnancy related depression and/or anxiety.
      In contrast with other psychiatric disorders, ED has rarely been studied in epilepsy. Using DSM-IV criteria we found slightly higher rates of ED than reported in non-pregnant patients with epilepsy (5% point prevalence) [
      • Rai D.
      • Kerr M.P.
      • McManus S.
      • Jordanova V.
      • Lewis G.
      • Brugha T.S.
      Epilepsy and psychiatric comorbidity: a nationally representative population-based study.
      ]. Possibly, earlier estimates of ED in epilepsy did not include BED. In women without epilepsy, BED is the most common type of ED during pregnancy [
      • Bulik C.M.
      • Von Holle A.
      • Hamer R.
      • Knoph-Berg C.
      • Torgersen L.
      • Magnus P.
      Patterns of remission: continuation and incidence of broadly defined eating disorders during early pregnancy in the Norwegian Mother and Child Cohort Study (MoBa).
      ]. As reproductive health is negatively affected by ED [
      • Linna M.S.
      • Raevuori A.
      • Haukka J.
      • Suvisaari J.M.
      • Suokas J.T.
      • Gissler M.
      Reproductive health outcomes in eating disorders.
      ], a lower rate of ED in pregnant than in non-pregnant WWE is expected. This is supported by Reiter et al. who found an increased life-time prevalence of unspecified self-reported ED in pregnant WWE compared with other women in the same study sample (4.8% vs. 2.9%), but very few reported having such disorders during pregnancy (0.4% vs. 0.3%). Similarly, unspecified ED has been found in only 0.8% of women without epilepsy after delivery [
      • Navarro P.
      • Garcia-Esteve L.
      • Ascaso C.
      • Aguado J.
      • Gelabert E.
      • Martin-Santos R.
      Non-psychotic psychiatric disorders after childbirth: prevalence and comorbidity in a community sample.
      ].
      The subgroup of WWE with ED had a numerically higher risk than the rest of the epilepsy cohort for the majority of pregnancy and delivery complications investigated. However, the power to find an ED related difference surpassed 60% only for peripartum depression and/or anxiety as well as operative deliveries. Our results were probably driven by BED. This disorder increases the risk for complications during pregnancy and delivery, and adverse birth outcome, such as higher birth weight babies, higher risk of large for gestational age and caesarian section than the referent [
      • Bulik C.M.
      • Von Holle A.
      • Siega-Riz A.M.
      • Torgersen L.
      • Lie K.K.
      • Hamer R.M.
      • et al.
      Birth outcomes in women with eating disorders in the Norwegian Mother and Child Cohort Study (MoBa).
      ].
      There are several explanations as to why WWE with ED have more pregnancy complications. Women with ED are more likely to smoke during pregnancy [
      • Bulik C.M.
      • Von Holle A.
      • Hamer R.
      • Knoph-Berg C.
      • Torgersen L.
      • Magnus P.
      Patterns of remission: continuation and incidence of broadly defined eating disorders during early pregnancy in the Norwegian Mother and Child Cohort Study (MoBa).
      ]; this is why we adjusted for this in our binary logistic regression model. Comorbid anxiety, depression and excessive weight gain may be associated with adverse effects on pregnancies and birth outcome [
      • Haugen M.
      • Brantsæter A.L.
      • Winkvist A.
      • Lissner L.
      • Alexander J.
      • Oftedal B.
      • et al.
      Associations of pre-pregnancy body mass index and gestational weight gain with pregnancy outcome and postpartum weight retention: a prospective observational cohort study.
      ,
      • Field T.
      • Diego M.
      • Hernandez-Reif M.
      • Figueiredo B.
      • Deeds O.
      • Ascencio A.
      • et al.
      Comorbid depression and anxiety effects on pregnancy and neonatal outcome.
      ]. Furthermore, the use of AEDs is a risk factor for pregnancy complications [
      • Borthen I.
      • Eide M.G.
      • Veiby G.
      • Daltveit A.K.
      • Gilhus N.E.
      Complications during pregnancy in women with epilepsy: population-based cohort study.
      ,
      • Veiby G.
      • Daltveit A.K.
      • Schjølberg S.
      • Stoltenberg C.
      • Øyen A.S.
      • Vollset S.E.
      • et al.
      Exposure to antiepileptic drugs in utero and child development: a prospective population-based study.
      ], and partly mediated the risk for operative deliveries in WWE and ED in our data.
      The prospective design of the MoBa study minimized reporting bias. The participation rate of 40.6% at first assessment is expected for population-based studies [
      • Nohr E.A.
      • Frydenberg M.
      • Henriksen T.B.
      • Olsen J.
      Does low participation in cohort studies induce bias?.
      ]. A study investigating selection bias found that epilepsy prevalence was similar in the MoBa study and in the general Norwegian population [
      • Nilsen R.M.
      • Vollset S.E.
      • Gjessing H.K.
      • Skjaerven R.
      • Melve K.K.
      • Schreuder P.
      • et al.
      Self-selection and bias in a large prospective pregnancy cohort in Norway.
      ].

      5. Conclusion

      The increased risk for complications in WWE with ED during pregnancy with possible adverse health effects for both mother and child should be considered and minimized in consultations both before and during pregnancy.

      Conflict of interest statement

      Eivind Kolstad has no conflicts of interest. Marte Helene Bjørk and Gyri Veiby have received lecture honoraria from Glaxo Smith Kline and congress travel support from UCB pharma. N.E. Gilhus has received lecture fee from Octapharma, Baxter, and Merck Serono.

      Acknowledgements

      MoBa is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/NIEHS (contract no. N01-ES-75558), NIH/NINDS (Grant No. 1 UO1 NS 047537-01 and Grant No. 2 UO1 NS 047537-06A1 ). We are grateful to all the participating families in Norway who take part in this on-going cohort study.

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