Published Ahead of Print on August 10, 2018 as 10.1212/WNL.

0000000000006173
ARTICLE

Unintended pregnancy, prenatal care, newborn

outcomes, and breastfeeding in women with
epilepsy
Emily L. Johnson, MD, Anne E. Burke, MD, MPH, Anqi Wang, MHS, and Page B. Pennell, MD Correspondence

®
Dr. Johnson
Neurology 2018;00:1-9. doi:10.1212/WNL.0000000000006173 ejohns92@jhmi.edu

Abstract
Objective
To compare the proportions of unintended pregnancies, prenatal vitamin or folic acid (PNVF)
use, adequate prenatal care visits, and breastfeeding among women with epilepsy (WWE) to
women without epilepsy (WWoE).

Methods
The Pregnancy Risk Assessment Monitoring System (PRAMS) is an annual survey of randomly
sampled postpartum women administered by the Centers for Disease Control and Prevention.
We used PRAMS data from 13 states from 2009 to 2014 to compare the primary outcomes in
WWE and WWoE, as well as our secondary outcomes of contraception practices, newborn
outcomes, and time to recognition of pregnancy. We adjusted for maternal age, race, ethnicity,
and socioeconomic status (SES), and we calculated odds ratios for these outcomes using
logistic regression.

Results
This analysis included 73,619 women, of whom 541 (0.7%) reported epilepsy, representing
3,442,128 WWoE and 26,635 WWE through weighted sampling. In WWE, 55% of pregnancies
were unintended compared to 48% in WWoE. After adjustment for covariates, epilepsy was not
associated with unintended pregnancy or with inadequate prenatal care. WWE were less likely
to report breastfeeding but more likely to report daily PNVF use. Newborns of WWE had
higher rates of prematurity.

Conclusions
Although planning for pregnancy is of utmost importance for WWE, more than half the
pregnancies in WWE were unintended. Maternal age and SES differences likely contribute to
the higher rates in WWE compared to WWoE. The proportion of women reporting breast-
feeding is lower in WWE despite studies indicating the safety of breastfeeding in WWE.

From the Department of Neurology (E.L.J.) and Department of Gynecology and Obstetrics (A.E.B.), Johns Hopkins School of Medicine, Baltimore; Johns Hopkins Bloomberg School of
Public Health (A.E.B., A.W.), Baltimore, MD; and Department of Neurology (P.B.P.), Brigham and Women’s Hospital, Boston, MA.

Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Copyright © 2018 American Academy of Neurology 1

Copyright ª 2018 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
 Glossary
AED = antiepileptic drug; CDC = Centers for Disease Control and Prevention; CI = confidence interval; IUD = intrauterine
device; MCM = major congenital malformation; NEAD = Neurodevelopmental Effects of Antiepileptic Drugs; NES =
nonepileptic seizures; NICU = neonatal intensive care unit; OR = odds ratio; PNVF = prenatal vitamin or folic acid; PRAMS =
Pregnancy Risk Assessment Monitoring System; SES = socioeconomic status; SGA = small for gestational age; WIC = Women,
Infants, and Children; WWE = women with epilepsy; WWoE = women without epilepsy.

Children born to women with epilepsy (WWE) on anti- Methods

epileptic drugs (AEDs) are at increased risk for adverse
outcomes, including major congenital malformations
(MCMs),1,2 neurodevelopmental delays,3 and low birth
weights.4 AED use and dose before conception influence
these risks; some AEDs such as valproic acid have sub-
stantially higher risks of these outcomes (with a dose-
dependent effect), while others have much lower risks of
adverse outcomes.1 Thus, pregnancy planning is of utmost
importance for WWE to ensure AED optimization before
pregnancy. However, because some AEDs interact with
hormonal contraceptives, WWE may be at increased risk
for unintended pregnancies.5 Although breastfeeding is
generally thought to be safe for WWE,6 some women are
still actively discouraged from breastfeeding while taking
AEDs.6 Prenatal vitamin or folic acid (PNVF) use before
conception and adequate prenatal care are also vital
in WWE.
One study of 1,144 WWE who self-enrolled in a birth
control registry and completed a retrospective survey
found that 65% of reported pregnancies in WWE were
unintended.7 In this group, younger women, racial minor-
ities, and Hispanic women had higher proportions of un-
intended pregnancies. In a survey of 148 reproductive-age
WWE cared for in a tertiary medical center, 50.3% of the
181 reported pregnancies in 77 women had been
unplanned.8
However, no comparisons have been made of unintended
pregnancies in a population including both WWE and
women without epilepsy (WWoE), which limits the con-
clusions that can be drawn about the effects of epilepsy per
se vs the effects of maternal age, race, and socioeconomic
status (SES). Much of the knowledge about WWE and
pregnancy outcomes has been obtained through careful
population-based studies, particularly from European
countries.9–11 To the best of our knowledge, no US
population–based studies have examined breastfeeding,
pregnancy intention, or PNVF use. Therefore, to de-
termine whether the prevalence of unintended pregnancy
and other outcomes is different between WWE and WWoE,
we compared the proportions of unintended pregnancies,
PNVF use, prenatal care, and breastfeeding in WWE and
WWoE, adjusting for age, race, ethnicity, and SES, in
a rigorously sampled population. Our secondary outcomes
were contraceptive practices, time to recognition of preg-
nancy, and neonatal outcomes.
The Centers for Disease Control and Prevention (CDC)
conducts the standardized Pregnancy Risk Assessment
Monitoring System (PRAMS), an ongoing survey-based
surveillance program of women during the postpartum period
(sampled from birth certificate data). PRAMS surveys are
currently administered in 47 states in English and Spanish,
representing ≈83% of all live births in the United States.12
Each state samples between 1,300 and 3,400 women annually,
depending on population. PRAMS uses stratified, weighted
population sampling to ensure that adequate data are available
for some high-risk populations (e.g., neonates with low birth
weight, mothers with advanced maternal age). The number of
targeted respondents in each category (e.g., low-birth-weight
infants born to mothers in a rural area) is determined from the
number of births in each category, proportion of all births that
each category represents, and predicted response rates, ad-
justed by the finite population correction when necessary.
Each participant has a weight assigned by the CDC according
to the representative population-based geographic and de-
mographic sampling.
Data are collected via mailed survey ≈3 months postpartum.
Multiple contacts (mailing and telephone) are attempted to
maximize participation; participation rates are >65% in most
states. The PRAMS survey consists of a set of core questions
administered by every state and optional standardized questions
(available at cdc.gov/prams/questionnaire.htm). From 2009 to
2014 (the most recent PRAMS data available at time of data
analysis), 13 centers asked mothers whether they carried a di-
agnosis of epilepsy or seizures in the 3 months before their
pregnancy.
We conducted a retrospective analysis using deidentified
data from the 12 states and 1 city that collected self-
reported epilepsy status through PRAMS (Delaware,
Hawaii, Florida, Maryland, Michigan, Minnesota, Missouri,
New York City, Utah, Washington, Wisconsin, West Vir-
ginia, and Wyoming).
Our primary outcomes were intendedness of pregnancy, daily
preconception use of PNVF, adequate prenatal care (assessed
with the Kotelchuck13 index, with inadequate care defined as
<50% of recommended visits, intermediate care as 50%–79%
of recommended visits, adequate care as 80%–110% of rec-
ommended visits, and “adequate-plus” care as >110% of
recommended visits), and any breastfeeding. Outcomes were

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taken from responses to the PRAMS questionnaire;
respondents indicated whether pregnancy was intended,
whether and how often they took a PNVF in the month
before pregnancy, at what gestational age they had their first
prenatal visit, how many prenatal visits they had, and whether
they breastfed at any time postpartum. Secondary outcomes
were approximate gestational age at which pregnancy was
recognized, neonatal outcomes (neonatal intensive care unit
[NICU] admission, small for gestational age [SGA; weight
<10th percentile for age], and premature birth [<37 weeks]),
birth control methods used at the time of conception, and
birth control methods used after delivery.
The covariates in our analysis were age, self-reported race
(white, black, Asian, Native American, other), ethnicity
(Hispanic or not Hispanic), and SES factors: yearly house-
hold income, use of Medicaid, and use of Women, Infants, and
Children (WIC) during pregnancy.
We excluded women missing data on history of epilepsy or
covariates or with age <12 or >50 years from primary analysis.
We conducted sensitivity analyses comparing the results of
analyses including women of all age values and including
those missing data on history of epilepsy covariates (race,
ethnicity, income) with dummy categorical variables used for
the missing variables.
We used Stata 15.0 (StataCorp, College Station, TX) to ac-
count for the survey sampling methodology applied by
PRAMS with multiple strata and sample weights. We first
compared participant characteristics of WWE and WWoE
with univariate analysis (using χ 2 or t tests as appropriate) and
univariate logistic regression for unadjusted odds ratios
(ORs). For categorical independent variables such as race, the
category with the largest number of respondents was selected
Results
This study included 73,619 women, of whom 548 (0.7%)
reported epilepsy (WWE). As a result of the proportional
stratified, weighted sampling described above, these sampled
women represent a population of 3,442,128 WWoE and
26,635 WWE (0.7% with epilepsy).
WWE were younger than WWoE (p = 0.001), had lower
household incomes (p < 0.001), and were more likely to be on
WIC or Medicaid (p < 0.001; table 1). WWE had a younger
mean age than WWoE for pregnancies reported as intended
and as unintended (p = 0.001). There was no difference in
race between WWE and WWoE.
Pregnancy intention
In WWE, 54.6% of pregnancies were unintended, which was
higher than the 47.6% of pregnancies that were unintended
in WWoE. WWE had an unadjusted OR of 1.40 for un-
intended pregnancy compared to WWoE (95% CI
1.18–1.66, p < 0.001). Unintended pregnancies were more
common in women with younger ages (p < 0.001), with
pregnancies most likely to be unintended in the <20-year-old
age group and most likely to be intended in the 30- to 34-
year-old group. Unintended pregnancies were more com-
mon in women with lower income; pregnancies were most
likely to be intended in the group with annual household
income >$50,000 (p < 0.001). Use of Medicaid or WIC was
also associated with unintended pregnancy (p < 0.001).
Table 1 Characteristics of WWE and WWoE
WWoE
WWE (n = 548), (n = 73,071), p
mean or % mean or % Value

as the reference group. We then used multivariable logistic Age, y 27.1 28.6 0.001
regression to adjust for the confounders of age, race, and SES
Race, % 0.827
and to estimate the ORs and 95% confidence intervals (CIs)
for the outcomes of interest in WWE compared to WWoE. White 70.3 67.6
For comparisons of continuous outcomes, we used a t test. A Black 15.9 15.9
value of p < 0.05 was considered significant.
Asian 6.7 8.3

Data availability Other 5.3 6.7

Limited PRAMS data are publically available at cdc.gov/
Hispanic ethnicity, % 8.0 12.5 0.056
prams/index.htm. Full PRAMS data are available to researchers
who submit a project application, abstract, and data-sharing Annual household 0.001
income, %
agreement to the CDC.
≤$15,000 44.3 26.4

Standard protocol approvals, registration, and $15,001–$25,000 13.8 15.3

patient consents
$25,001–$50,000 16.9 22.4
The PRAMS program is approved by the Institutional Re-
view boards of each participating state and of the CDC. This >$50,000 25.2 35.9
study was approved by the central PRAMS proposals com- WIC or Medicaid use 65.9 52.7 <0.001
mittee and separately by the Florida Department of Health
Institutional Review Board and was reviewed and de- Abbreviations: WIC = Women, Infants, and Children supplemental nutrition
program; WWE = women with epilepsy; WWoE = women without epilepsy.
termined to be exempt by the Johns Hopkins Institutional Values are means or percentages of respondents.
Review Board.

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 Pregnancies were most likely to be intended in Asian and
white participants and least likely to be intended in Native
American, black, or other race participants. Pregnancies were
less likely to be intended in Hispanic than in non-Hispanic
participants (p < 0.001).
After adjustment for age, race, ethnicity, and SES (income
and WIC or Medicaid use), epilepsy was not associated
with unintended pregnancy (OR 1.00, 95% CI 0.76–1.32, p
= 0.989; table 2). Higher income, age of 30 to 34 years, and
no use of Medicaid or WIC were all associated with
pregnancy intention in multivariable analysis (table 2).
Although the proportion of intended pregnancies varied
by state (with intended pregnancies least common in
Hawaii after adjustment for covariates), there was no
interaction between state and epilepsy (i.e., results of as-
sociation of epilepsy with pregnancy intention did not
differ by state).
Breastfeeding
We found that 69.1% of WWE reported breastfeeding at any
time compared to 84.6% of WWoE (OR 0.40, 95% CI
0.30–0.55, p < 0.001). After adjustment for covariates, WWE
remained less likely to report any breastfeeding than WWoE
(OR 0.42, 95% CI 0.26–0.68, p < 0.001; table 3). Higher
income, Asian and other race, Hispanic ethnicity, and no use
of Medicaid or WIC were associated with breastfeeding.
Among women who reported breastfeeding, there was no
difference in the length of time that infants were breastfed: the
mean was 6.6 weeks in WWoE compared to 6.4 weeks in
WWE (p = 0.607). There was no interaction between state
and epilepsy.

Table 2 Adjusted ORs for unintended pregnancy

compared to intended pregnancy
Table 3 Adjusted ORs for reporting breastfeeding
Adjusted OR for unintended p compared to not reporting breastfeeding
Characteristic pregnancy (95% CI) Value
Adjusted OR for
WWE (compared to 1.00 (0.76–1.32) 0.989 Characteristic Breastfeeding (95% CI) p Value
WWoE)
WWE (compared to WWoE) 0.42 (0.26–0.68) <0.001
Age, y
Age, y
<20 3.01 (2.62–3.47) <0.001
<20 0.71 (0.57–0.89) 0.003
20–24 1.50 (1.39–1.61) <0.001
20–24 0.87 (0.75–1.00) 0.053
25–29 1.0 (Reference group)
25–29 1.0 (Reference group)
30–34 0.92 (0.86–0.99) 0.023
30–34 1.08 (0.92–1.24) 0.327
35–39 1.09 (1.00–1.18) 0.049
35–39 0.98 (0.82–1.17) 0.843
≥40 1.26 (1.12–1.42) <0.001
≥40 0.78 (0.59–1.03) 0.081
Race
Race
White 1.0 (Reference group)
White 1.0 (Reference group)
Black 2.05 (1.92–2.19) <0.001
Black 0.81 (0.72–0.92) 0.001
Asian 0.95 (0.86–1.04) 0.268
Asian 1.33 (1.09–1.63) 0.006
Native American 0.75 (0.65–0.87) <0.001
Native American 1.33 (0.93–1.92) 0.121
Other 1.11 (0.99–1.25) 0.080
Other 1.38 (1.04–1.83) 0.025
Hispanic ethnicity 0.98 (0.89–1.07) 0.651
Hispanic ethnicity 2.02 (1.66–2.46) <0.001
Annual household
income, $ Annual household income, $

≤15,000 0.58 (0.54–0.63) <0.001 ≤15,000 0.59 (0.51–0.69) <0.001

15,001–25,000 0.73 (0.68–0.79) <0.001 15,001–25,000 0.89 (0.75–1.06) 0.187

25,001–50,000 1.0 (Reference group) 25,001–50,000 1.0 (Reference group)

>50,000 1.66 (1.53–1.79) <0.001 >50,000 1.14 (0.95–1.37) 0.164

WIC or Medicaid use 0.60 (0.56–0.64) <0.001 WIC or Medicaid use 0.51 (0.43–0.61) <0.001

Abbreviations: CI = confidence interval; OR = odds ratio; WIC = women,
infants, and children supplemental nutrition program; WWE = women with
epilepsy; WWoE = women without epilepsy.
OR for WWE compares unintended pregnancy in WWE to WWoE. ORs are
adjusted for all covariates in table.
Abbreviations: CI = confidence interval; OR = odds ratio; WIC = Women,
Infants, and Children supplemental nutrition program; WWE = women with
epilepsy; WWoE = women without epilepsy.
OR for WWE compares breastfeeding in WWE to WWoE. ORs are adjusted for
all covariates in table.

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Vitamin use and prenatal care 0.202); WWE had more adequate-plus prenatal care (>110%
The majority (52.3%) of women reported no preconception of recommended prenatal visits; adjusted OR 1.50, 95% CI
PNVF use, and only 43.6% of WWE and 31.8% of WWoE 1.00–2.27, p = 0.051; table 5), although this was not a statis-
reported daily PNVF use. After adjustment for covariates, tical difference. Women <20 years of age, those with income
WWE were more likely to report daily PNVF use before <$25,000, women of races other than white or other, and
conception than were WWoE (OR 2.03, 95% CI 1.31–3.13, p women with WIC/Medicaid use were less likely to have at
= 0.002). PNVF use was more common in women with in- least adequate prenatal care.
creasing age, race other than black or Asian, and higher
incomes and without Medicaid or WIC use (table 4). There WWE reported being sure that they were pregnant at a mean
was an interaction between state and epilepsy: PNVF was of 6.5 weeks’ gestational age (median 5 weeks, interquartile
reported less among WWE in Delaware, Florida, Maryland, range 4–8 weeks, range 1–24 weeks). After adjustment for
Utah, Wisconsin, and West Virginia than in other states. covariates, there was no difference at time of pregnancy rec-
ognition between WWE and WWoE, who recognized they
WWE and WWoE were equally likely to have at least adequate were pregnant at a mean of 5.9 weeks.
prenatal care (adjusted OR 0.74, 95% CI 0.47–1.17, p =
Contraception before pregnancy
and postpartum
Table 4 Adjusted ORs for reported daily use of PNVF in A large proportion (44.5%) of the 34,220 women who
the month before pregnancy compared to responded to queries on contraception reported using some
reporting less than daily use of PNVF
method of birth control when they became pregnant. Detailed
Adjusted OR for daily information on the type of birth control used before con-
PNVF use before
Characteristic conception (95% CI) p Value
ception was available in 5.6% (4,135) of WWoE and 7.2%
(39) of WWE (table 5). The most commonly cited methods
WWE (compared to WWoE) 2.03 (1.31–3.13) 0.002 of birth control used at the time of conception were condoms
Age, y (70.2% of WWE, 49.4% of WWoE) and withdrawal (38.5% of
WWE, 42.6% of WWoE). No WWE reported using in-
<20 0.56 (0.43–0.71) <0.001
trauterine devices (IUDs) or contraceptive implants at the
20–24 0.78 (0.69–0.88) <0.001 time of conception. There was no difference in the use of
25–29 1.0 (Reference group) hormonal birth control at the time of conception (pill, ring,
injectable, patch, implant) by WWE (31.6%) and WWoE
30–34 1.24 (1.13–1.37) <0.001
(30.7%) (table 6).
35–39 1.27 (1.13–1.43) <0.001

≥40 1.46 (1.21–1.77) <0.001

After delivery, the majority of women (82.6%) reported using
birth control (table 6). Condoms were the most common
Race form of postpartum birth control reported by both WWE and
White 1.0 (Reference group) WWoE. The proportion of WWE reporting a long-acting or
permanent birth control method after delivery was 35.8%,
Black 0.70 (0.59–0.74) <0.001
including 17.6% reporting an IUD. Among WWoE, 28%
Asian 0.75 (0.66–0.86) <0.001 reported a long-acting or permanent birth control after de-
Native American 0.87 (0.66–1.15) 0.325
livery, including 16.8% reporting an IUD.

Other 0.90 (0.74–1.09) 0.289

Neonatal Outcomes
Hispanic ethnicity 0.92 (0.80–1.06) 0.264 In univariate analysis, epilepsy was associated with higher
rates of prematurity (p < 0.001), NICU stay (p < 0.001), and
Annual household income, $
SGA (p < 0.001). In multivariable analysis, epilepsy was as-
≤15,000 0.74 (0.65–0.84) <0.001 sociated with a higher risk of prematurity (adjusted OR 1.63,
15,001–25,000 0.82 (0.72–0.94) 0.004 95% CI 1.23–2.16), although not with SGA or with NICU
stay after adjustment for prematurity. In univariate analysis,
25,001–50,000 1.0 (Reference group)
unintended pregnancies were more likely than intended
>50,000 1.58 (1.43–1.76) <0.001 pregnancies to result in a neonate that was SGA (p < 0.001) or
WIC or Medicaid use 0.62 (0.56–0.69) <0.001
had NICU stay (p = 0.023); there was no difference in pre-
maturity (p = 0.249). After adjustment for epilepsy and de-
Abbreviations: : CI = confidence interval; PNVF = prenatal vitamins, vitamins, mographics, there were no interactions between epilepsy and
or folic acid; OR = odds ratio; WIC = Women, Infants, and Children supple-
mental nutrition program; WWE = women with epilepsy; WWoE = women pregnancy intention for neonatal outcomes.
without epilepsy.
OR for WWE compares daily PNVF use in WWE to WWoE. ORs are adjusted
for all covariates in the table. In sensitivity analyses, results including women with missing
epilepsy history (7,482 of 73,619) and of all reported ages (n

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 Table 5 Adjusted ORs for at least adequate prenatal care (compared to less than adequate prenatal care) and for
adequate-plus prenatal care (compared to less than adequate and adequate prenatal care)
Adjusted OR for at least adequate Adjusted OR for adequate-plus
Characteristic prenatal care (95% CI) p Value prenatal care (95% CI) p Value

Women with epilepsy (compared to WWoE) 0.74 (0.47–1.17) 0.202 1.50 (1.00–2.27) 0.051

Age, y

<20 0.68 (0.56–0.83) <0.001 1.00 (0.82–1.22) 0.982

20–24 0.90 (0.80–1.01) 0.078 0.91 (0.82–1.02) 0.117

25–29 1.0 (Reference group) 1.0 (Reference group)

30–34 0.98 (0.87–1.10) 0.682 1.00 (0.91–1.10) 0.977

35–39 0.95 (0.83–1.09) 0.485 1.13 (1.00–1.28) 0.045

≥40 0.98 (0.78–1.24) 0.893 1.17 (0.96–1.42) 0.119

Race

White 1.0 (Reference group) 1.0 (Reference group)

Black 0.57 (0.51–0.64) <0.001 0.87 (0.78–0.97) 0.011

Asian 0.68 (0.59–0.77) <0.001 0.75 (0.65–0.86) <0.001

Native American 0.71 (0.54–0.94) 0.016 1.00 (0.77–1.32) 0.961

Other 0.85 (0.70–1.03) 0.088 0.93 (0.77–0.98) 0.419

Hispanic ethnicity 0.87 (0.76–1.01) 0.069 0.85 (0.74–0.98) 0.024

Annual household income

≤15,000 0.66 (0.58–0.75) <0.001 0.96 (0.85–1.09) 0.537

15,001–25,000 0.84 (0.73–0.97) 0.016 1.06 (0.93–1.20) 0.382

25,001–50,000 1.0 (Reference group) 1.0 (Reference group)

>50,000 0.95 (0.83–1.09) 0.461 1.02 (0.91–1.14) 0.725

WIC or Medicaid use 0.86 (0.75–0.98) 0.020 1.09 (0.98–1.22) 0.110

Abbreviations: CI = confidence interval; OR = odds ratio; WIC = Women, Infants, and Children supplemental nutrition program; WWE = women with epilepsy;
WWoE = women without epilepsy.
OR for WWE compares adequate or adequate-plus prenatal care in WWE to WWoE. ORs are adjusted for all covariates in table.

= 5 with age <12 years, n = 749 with age >50 years) and
including women with missing covariates (race, n = 580;
ethnicity, n = 16,090; income, n = 16,548) were similar.
Discussion
The proportion of WWE in our study population is 0.7%, which
falls within the accepted estimates of the prevalence of epilepsy
as 4 to 10 per 1,000 adults.14 We found that 55% of pregnancies
in WWE were unintended but that epilepsy was not a risk factor
for unintended pregnancy after adjusting for age, race, ethnicity,
and SES. After adjusting for covariates, we found that WWE
were less likely to breastfeed than were WWoE, but they had
higher proportions of daily preconception PNVF use.
Unplanned pregnancies have been associated with higher
health care costs and a risk of adverse infant and maternal
outcomes,15 although in this study we found no association
with prematurity, SGA, or NICU stay after adjusting for de-
mographics and epilepsy. Ideally, unintended pregnancies
would be lower in WWE than in WWoE, given the impor-
tance of pregnancy planning and optimization of AED med-
ication regimen and dose before pregnancy because of the
risks for MCM, low birth weight, and cognitive deficits as-
sociated with some AEDs.
Our findings are complementary to those from the self-
selecting Epilepsy Birth Control Registry that 65% of preg-
nancies in WWE were unintended and that 78% of WWE
treated at a tertiary epilepsy center had ever had an un-
intended pregnancy.7 Because our study reports intention
regarding only the woman’s most recent pregnancy, some
WWE may have had unintended pregnancies in the past.
Similar to our study, the Epilepsy Birth Control Registry study
also found that unintended pregnancies were more common
in younger WWE and racial minorities.7 Our results show that

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Table 6 Birth control methods reported at the time of conception and after delivery
Before conception After delivery

Method WWE %WWE WWoE %WWoE WWE %WWE WWoE %WWoE

Any 133/322 41.3 15,354/33,597 45.7 362/460 78.7a 47,021/56,886 82.7a

Condoms 26/37 70.3a 2,024/4,100 49.4a 56/187 30.0 7,744/22,610 34.2

Withdrawal 15/39 38.5 1,763/4,135 42.6 20/187 10.7 3,257/22,600 14.4

a
Abstinence 5/22 22.7 129/2,375 5.4* 21/187 11.2 2,185/22,602 9.7

Birth control pill 7/38 18.4 985/4,045 24.3 37/187 19.8 5,519/22,623 24.4

a
Injection 4/37 10.8 178/4,033 4.4 35/187 18.7 2,198/22,620 9.72a

Ring or patch 1/22 4.5 71/2,377 3.0 2/157 1.6 272/14,669 1.9

Rhythm/natural family planning 1/37 2.7 552/4,054 13.6 2/187 1.1a 980/22,598 4.3a

IUD 0/37 0 89/4,027 2.2 33/187 17.6 3,810/22,615 16.8

a
Implant 0/37 0 20/2025 0.5 11/187 5.9 692/22,609 3.1a

Tubal ligation 0/22 0 8/2,376 0.3 23/187 12.3a 1,833/22,610 8.1a

Abbreviations: IUD = intrauterine device; WWE = women with epilepsy; WWoE = women without epilepsy.
The number of women answering each question varied because some respondents skipped some questions.
a
p < 0.05 on χ2 comparison.

although WWE were more likely to have an unintended
pregnancy than were WWoE in the overall study population,
this association did not persist after controlling for age, race,
and SES factors. These findings indicate that the demographic
characteristics of WWE help explain the excess proportion of
unintended pregnancies among WWE.
WWE had a younger mean age than WWoE; this finding was
true for both intended and unintended pregnancies. Further
study of factors driving the childbearing choices and the birth
control choices of WWE is needed to investigate the reasons
for this finding. Future studies should also include clinical
details to allow stratification by epilepsy types and severity
and types of AEDs used, which are likely factors in both
intended and unintended pregnancies.
Breastfeeding has numerous documented health benefits to
both the infant and mother.16 The Norwegian Mother and
Child Cohort Study, a prospective study that included 223
mothers taking AEDs (including polytherapies), found im-
proved infant weight at 6 weeks in breastfed infants and
suggested a tendency toward improved motor and social skills
at 6 months in children who were breastfed for at least 6
months.10 The Neurodevelopmental Effects of Antiepileptic
Drugs (NEAD) study, a prospective multicenter observa-
tional study of women taking carbamazepine, lamotrigine,
phenytoin, and valproate, found higher IQ and cognitive
abilities in breastfed children of women taking these AEDs at
up to 6 years of age and found no adverse effects, supporting
the recommendation of breastfeeding for WWE who choose
to do so.6 In the current study, the proportion of 69.1%
reporting breastfeeding among WWE was lower than that in
WWoE (84.6%). Moreover, this disparity persisted after ad-
justment for covariates. This may indicate that WWE are less
likely to breastfeed their children because of concerns for the
effects of AEDs and that there is a need for continued edu-
cation of health care providers and patients on breastfeeding
safety in WWE. In the widely used resource Medications &
Mothers’ Milk, none of the 5 most commonly prescribed
AEDs in pregnancy17 receive the highest rating of compati-
bility with breastfeeding, despite the studies listed above.18 In
the NEAD study, 42.9% of WWE taking AEDs reported
breastfeeding at 3 months postpartum.6 The higher pro-
portion of WWE reporting any breastfeeding in the current
study is likely due to women who breastfed <3 months.
Folic acid is important for all women of childbearing potential,
who are advised to take at least 400 μg folic acid daily be-
ginning before pregnancy to reduce the risk of neural tube
defects and other adverse neonatal outcomes.19,20 This may
be especially important in WWE; in the NEAD study, peri-
conceptional folic acid use in WWE was associated with
higher child IQ at 6 years of age.3 Recent prospective data
from Norway showed a lower risk of autistic traits in children
of WWE taking AEDs if the mother took a periconceptional
folic acid supplement,9 although definitive evidence on
whether folic acid reduces MCMs in WWE is lacking. En-
couragingly, WWE were more likely to report daily PNVF use
before pregnancy than were WWoE after adjustment for
confounders. However, the majority (52.3%) of women
reported no PNVF use, and only 43.6% of WWE and 31.8% of
WWoE reported daily PNVF use. Continued public health
education and educational efforts by health care providers on
the importance of prenatal vitamins and folic acid are needed,

Neurology.org/N Neurology | Volume , Number  | Month 0, 2018 7

Copyright ª 2018 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
 as well as improved access for women who cannot afford them,
to increase the proportion of all women meeting this guideline.
The increased daily use of PNVF in WWE may reflect the fact
that WWE generally see a physician at least yearly for their
epilepsy and may receive extra education on the importance of
folic acid use given increased teratogenic (structural and neu-
rodevelopmental) risks in women on AEDs.
Prior studies have shown increased prematurity, neonatal
complications, and SGA in WWE4,11,21; in particular, the use
of topiramate has been linked to SGA infants.4,22 Similarly,
this study found a higher proportion of SGA, NICU stays, and
prematurity in neonates born to WWE; the association with
prematurity persisted after adjustment for covariates. These
outcomes were not the primary focus of our study, given the
lack of information on medications, number of seizures during
pregnancy, and other factors specific to epilepsy that may
influence neonatal outcomes.
After confounders were controlled for, WWE were equally
likely to report at least adequate prenatal care, suggesting that
epilepsy alone does not meaningfully limit women’s access to
prenatal care. A higher, but not statistically different, proportion
of WWE reported “supra-adequate” prenatal care compared to
WWoE. While standard “adequate” prenatal care is defined for
all pregnant women, WWE may require more visits because of
a concern for intrauterine growth restriction, MCMs, AED
blood level monitoring, and seizure control. WWE often see
a high-risk obstetrician and/or maternal–fetal medicine sub-
specialist because the risks of morbidity and mortality of
pregnancy and delivery are elevated in WWE compared to
WWoE.23,24 The number of visits observed in this study may
also reflect a concern for conditions leading to the increased
premature births, SGA, and NICU stays in WWE we observed.
In our study, pregnancy recognition occurred at a mean of 6.5
weeks’ gestational age in WWE, emphasizing the need for folate
supplementation and careful consideration of AED regimen,
e.g., avoiding valproic acid when alternatives exist, in all WWE
of childbearing potential (because pregnancy may not be rec-
ognized before some vital embryonic development).
A higher proportion of WWE (35.8%) reported using a long-
acting or permanent birth control method after delivery than
did WWoE (28.0%). The use of IUDs was similar in WWE
and WWoE, while the use of tubal ligation and implant was
higher in WWE. IUDs are often a preferred option for WWE
who desire a reversible form of birth control because of the
high effectiveness, reversibility, longevity, and absence of
hormonal interactions with AEDs.25–27 Whether the differ-
ences in the use of long-acting birth control are due to patient
choice, affordability, or counseling regarding long-acting
forms of birth control is unknown.
The strengths of this study include the large sample size,
rigorous sampling methodology, and use of a control group of
WWoE. This study also has several limitations. The PRAMS
8 Neurology | Volume , Number  | Month 0, 2018
Copyright ª 2018 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
study is a survey-based, cross-sectional study, and limitations
of the PRAMS methodology include recall and response bias
(although multiple attempts are made for each selected re-
spondent), incomplete data available for each woman (e.g.,
prescribed medications), limited generalizability because not
all states are represented, and lack of inclusion of women who
have experienced a spontaneous or therapeutic pregnancy
termination or stillbirth (because only live births are in-
cluded). Our specific study has limitations in that we rely on
women’s self-report of epilepsy, which may inappropriately
categorize WWE; however, the bias due to misclassification is
expected to be toward the null.28,29 Women of childbearing
age make up a large percentage of patients with nonepileptic
seizures (NES), and some may be included in WWE in this
study. However, on the basis of the estimated prevalence of 2
to 33 per 100,000 of patients with NES,30 of which up to 71%
are women of childbearing age,31 and on the estimated
number of WWE in the United States of 1.3 million, only 5.7%
of the women included in our WWE group are expected to
have NES; thus, our findings likely accurately represent WWE
in the included states. Another limitation is the lack of in-
formation about whether WWE had neurology or sub-
specialty care in addition to their obstetric and primary care
and on specific AEDs used. In addition, the subanalysis of
contraceptive use was limited by small cell size.
The majority of pregnancies in WWE are unintended. However,
after adjusting for age, race, ethnicity, and SES, we found no
increased proportion of unintended pregnancy among WWE
compared to WWoE. The proportion of women reporting
breastfeeding is lower in WWE, while daily preconception
PNVF use is higher in WWE; these findings persisted after
adjustment for covariates. Prospective studies of WWE are
needed to determine more accurate rates of unintended preg-
nancies, PNVF use, prenatal care, neonatal outcomes, and
breastfeeding. Effective education on the importance of preg-
nancy planning and folic acid use and the risk of unintentional
pregnancy is particularly needed in groups at higher risk. In
addition, continued education of WWE and health care pro-
viders who care for WWE (including neurologists, primary care
doctors, and obstetricians) is needed regarding the safety of
breastfeeding, which has been established in long-term follow-
up studies of cognition in children of WWE.6
Author contributions
Emily Johnson designed the study, obtained the data, con-
ducted preliminary analyses, and drafted the manuscript.
Anne Burke provided critical feedback on the study design
and substantially edited the manuscript for content. Anqi
Wang performed data analyses and substantially edited the
manuscript for content. Page B. Pennell provided critical
feedback on the study design and substantially edited the
manuscript for content.
Acknowledgment
The authors acknowledge the CDC and PRAMS working
group (CDC PRAMS Team, Applied Sciences Branch,
Neurology.org/N
Division of Reproductive Health) for providing access to the
PRAMS dataset used in this analysis.
Study funding
This study was supported with institutional funds (Johns
Hopkins Department of Neurology).
Disclosure
The authors report no disclosures relevant to the manuscript.
Go to Neurology.org/N for full disclosures.
Received January 24, 2018. Accepted in final form June 15, 2018.
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Neurology | Volume , Number  | Month 0, 2018 9
Unintended pregnancy, prenatal care, newborn outcomes, and breastfeeding in women
with epilepsy
Emily L. Johnson, Anne E. Burke, Anqi Wang, et al.
Neurology published online August 10, 2018
DOI 10.1212/WNL.0000000000006173

This information is current as of August 10, 2018

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