Journal of Midwifery & Women’s Health www.jmwh.

org
Review

Bipolar Disorder in Pregnancy: A Review

of Pregnancy Outcomes
CEU
Debra A. Scrandis, PhD, CRNP-F, CRNP-PMH

Introduction: Women with bipolar disorder may benefit from continuation of their medications during pregnancy, but there may be risks to the
fetus associated with some of these medications. This article examines the evidence relating to the effect of bipolar disorder and pharmacologic
treatments for bipolar disorder on pregnancy outcomes.
Methods: MEDLINE, CINAHL, ProQuest Dissertation & Theses, and the Cochrane Database of Systematic Reviews were searched for English-
language studies published between 2000 and 2017, excluding case reports and integrative reviews. Twenty articles that met inclusion criteria were
included in this review.
Results: Women with bipolar disorder have a higher risk for pregnancy complications and congenital abnormalities than do women without
bipolar disorder. In addition, illness relapse can occur if psychotropic medications are discontinued. There are limited data to recommend dis-
continuing lithium, lamotrigine, or carbamazepine during pregnancy. Valproic acid is not recommended during pregnancy due to increased odds
of neural tube defects associated with its use. Atypical antipsychotics are used more frequently during pregnancy, with mixed evidence regarding
an association between these agents and congenital malformations or preterm birth.
Discussion: The knowledge of benefits and risks of bipolar disorder and its treatment can help women and health care providers make indi-
vidualized decisions. Prenatal care providers can discuss the evidence about safety of medications used to treat bipolar disorder with women in
collaboration with their mental health care providers. In addition, women being treated for bipolar disorder require close monitoring for depressive
and manic/hypomanic episodes that impact pregnancy outcomes.
J Midwifery Womens Health 2017;62:673–683  c 2017 by the American College of Nurse-Midwives.

Keywords: antipsychotic agents, bipolar disorder, lithium, pharmacology, pharmacokinetics, pregnancy, pregnancy outcome, valproic acid

INTRODUCTION require at least one lifetime manic episode, defined as ab-

Bipolar disorder is a lifelong mental illness. Onset typically
occurs in early adulthood, which is also the beginning of the
childbearing years in women. Medications such as mood sta-
bilizers and atypical antipsychotics are used to decrease the
number of mood episodes, increase the length of time be-
tween episodes, provide neuroprotection, and improve over-
all function.1 Women with bipolar disorder require treatment
throughout life to obtain these goals. Bipolar symptoms can be
exacerbated during pregnancy and postpartum, yet there may
be fetal risks associated with continued use of psychotropic
maintenance drugs during pregnancy. It is critical that pre-
natal care providers are aware of the latest evidence about
treatments for bipolar disorder, their benefits, and their risks.
This article reviews the evidence regarding the effects of bipo-
lar disorder, mood stabilizers, and atypical antipsychotics on
pregnancy outcomes.
Background
The lifetime prevalence of bipolar disorder in the United
States is 4.4%.2 There are 2 types of bipolar disorder: bipo-
lar I and bipolar II. Bipolar disorder includes episodes of
depressive and manic/hypomanic symptoms that can occur
without warning. The criteria for the diagnosis of bipolar I
Address correspondence to Debra A. Scrandis, PhD, CRNP-F, CRNP-
PMH, 655 West Lombard Street Room 545C, Baltimore, MD 21201.
E-mail: dscra001@son.umaryland.edu
normal and expansive, elevated, or irritable mood with in-
creased activity or energy lasting at least one week. The cri-
teria for bipolar II are hypomanic episodes that include the
same symptoms as manic episodes but last at least 4 consec-
utive days and less than one week. Three of the following
additional symptoms are required to meet criteria for diag-
nosis of both types of bipolar disorder: inflated self-esteem,
decreased need for sleep, more talkative than usual, flight of
ideas/racing thoughts, distractibility, increase in goal-directed
activity, or excessive involvement in high-risk activities with
painful consequences.3 In women, bipolar II disorder is more
common than bipolar I.3 Despite the distinctions between
these 2 disorders, both are treated with mood stabilizers and
atypical antipsychotics.
The latest data suggest that the pathophysiology of bipolar
disorder includes disruptions in neurobehavioral systems,
neuron circuits, and neuroregulatory mechanisms. The de-
creased levels of neuroprotective brain-derived neurotropic
factor (BDNF), increased levels of neurodegeneration from
inflammation and oxidative stress, and failure of physio-
logic compensatory mechanisms over time contribute to
the illness’s progression.1 Risk factors associated with this
chronic progression include increased number of mood
episodes, early trauma history, and psychiatric comorbidity.4
Preliminary in vitro studies appear to suggest that estro-
gen and progesterone improve BDNF levels and decrease
oxidative stress and inflammation, so fluctuations in the
levels of these ovarian hormones may contribute to the high
risk of relapse postpartum and at other times in women’s

1526-9523/09/$36.00 doi:10.1111/jmwh.12645 c 2017 by the American College of Nurse-Midwives

 673
 ✦ Women with bipolar disorder have an increased risk for pregnancy complications.
✦ There is mixed evidence to support discontinuation of maintenance medications for women with bipolar disorder, with
the exception of valproic acid, which is not recommended for use by pregnant women.
✦ Prenatal care providers can have individualized discussions with women regarding their mental health in addition to neona-
tal risks from bipolar disorder and/or medications used to treat bipolar disorder.
✦ Women benefit from prenatal care providers’ close collaboration with their mental health care providers during pregnancy.

reproductive cycles, periods when the 2 hormones are at an
ebb.5
The retrospective analysis of episodes of mood disorders
during pregnancy and postpartum by Viguera et al6 found that
women with bipolar disorder (n = 621) had a higher risk of ill-
ness episodes in pregnancy (relative risk [RR], 4.85; 95% con-
fidence interval [CI], 3.32–7.32) and the postpartum period
(RR, 2.10; 95% CI, 1.77–2.50) compared with women with
unipolar depression (n = 541). A recent systematic review7 as-
sessed the risk of postpartum relapse in women with bipolar
disorder and women with postpartum psychosis in an anal-
ysis of 37 studies (N = 5700 births). Five studies had infor-
mation on prenatal use of medication, and in these data, the
authors found that women who used prophylactic medica-
tions during pregnancy had a significantly lower relapse rate
(n = 60, 23%; 95% CI, 14%-27%) compared with women
who did not take medications during pregnancy (n = 385,
66%; 95% CI, 57%-75%; P ⬍ .001). Newport et al8 (n = 26)
also found that women who discontinued the mood stabilizer
lamotrigine (Lamictal) during pregnancy had more illness re-
lapses (100%) than women who continued lamotrigine (30%).
There are also concerns about pregnancy outcomes when
psychotropic medications are continued during gestation. It
is well documented that valproic acid (Depakote) increases
the risk of neural tube defects, major and minor malfor-
mations, and neurodevelopment impairments in exposed fe-
tuses and thus is not recommended for use by childbearing
women.9–11 Lithium has been implicated in an increased inci-
dence of Ebstein’s anomaly.12 There are emerging data about
the pregnancy-related effects of other treatments for bipo-
lar disorder, including lamotrigine, carbamazepine (Tegretol),
and atypical antipsychotics. Two questions are addressed in
this review: 1) What is the impact of the diagnosis of bipo-
lar disorder itself on pregnancy outcomes? and 2) What is the
impact of pharmacologic treatments for bipolar disorder on
pregnancy outcomes?
METHODS
To examine the associations between bipolar disorder,
psychotropic medications, and pregnancy outcomes, a search
was conducted in MEDLINE, CINAHL, ProQuest Disser-
tation & Theses, and the Cochrane Database of Systematic
Reviews. The search was supplemented by reference track-
ing of selected articles. To be included in the review, ar-
ticles had to meet the following criteria: written in En-
glish; published between January 2000 and January 2017;
systematic reviews with or without meta-analyses; and stud-
ies that address relationships among bipolar disorder, psy-
chotropic medications, and pregnancy outcomes. The search
terms used were pregnancy complications, bipolar disorder,
pregnancy outcomes, lithium, valproic acid, lamotrigine,
second-generation antipsychotics, childbearing, and med-
ications (Figure 1).
The search yielded 379 articles. Abstracts were reviewed
after removing duplicate articles. Forty-two records were
screened, and full-text articles were obtained. Articles were
excluded if they were case reports (n = 9), integrated liter-
ature reviews (n = 3), or studies with findings reported in
systematic reviews (n = 6).
Systematic review quality was evaluated using the Revised
Assessment of Multiple Systematic Reviews (R-AMSTAR)
by Kung et al.13 This rating instrument yields a total score
between 14 and 44. The authors recommend scores above
22 to signify quality. The quality of cohort and case-control
studies was examined using the Newcastle-Ottawa Quality
Assessment Scale.14 The scale ranges from 0 to 9, with 0 being
the lowest quality, and focuses on these criteria: selection of
case or cohort (0–4 points), comparability between case and
control groups (0–2 points), and the analysis of outcomes
(0–3 points). The comparability criterion related to whether
the study controlled for confounding factors. Fourteen stud-
ies were included in this review that had scores ranging from
6 to 9. Articles scoring below 6 were excluded. Following
the rating process, 20 articles met the inclusion criteria,
including 5 systematic reviews,15–19 12 cohort studies,20–31
2 case-control studies,11,32 and one meta-analysis.33
RESULTS
Impact of Bipolar Disorder on Pregnancy Outcomes
Rusner et al15 conducted a systematic review of studies to ex-
amine pregnancy outcomes in women with bipolar disorder.
The authors analyzed the results of studies29,31,34 (N = 79,358)
and found that compared with women without bipolar dis-
order, women with bipolar disorder had an increased risk
of preterm birth (10.68% vs 6.12%, respectively; odds ratio
[OR], 1.83; 95% CI, 1.64–2.06). Of the studies that assessed for
congenital anomalies, one found no increased risk in women
with bipolar disorder,20 but these findings were not included
in the meta-analysis because the cohort in the study was
dissimilar from those in the other 2 studies. The studies29,31
that did inform the meta-analysis found an increased risk

674 Volume 62, No. 6, November/December 2017

 Records identified through
database searching
(n=374)
Records after duplicates removed
(n=200)
Records screened
(n=42)
Full-text articles
assessed for eligibility
(n=42)
Studies included in
qualitative synthesis
(n=20)
Figure 1. PRISMA Flow Diagram.
of congenital abnormalities in women with bipolar disorder
(4.34% vs 2.83%, respectively; OR, 1.56; 95% CI, 1.34–1.82)
compared with women without bipolar disorder. They found
no increased risk of having a newborn who was small for
gestational age (OR, 1.07; 95% CI, 0.96–1.21). Although the
odds ratio for small for gestational age was not significant
overall, women with bipolar disorder were more likely to
have a newborn who was severely small for gestational age
(defined as below the third percentile) compared with women
without bipolar disorder (OR, 1.31; 95% CI, 1.08–1.58).
Boden et al29 examined pregnancy outcome data from
a mostly Swedish cohort (N = 332,137), comparing women
without bipolar disorder, women with bipolar disorder who
continued their mood stabilizers during pregnancy (lithium,
antipsychotics, carbamazepine, lamotrigine, or valproate),
and women with bipolar disorder who discontinued their
mood stabilizers. This analysis found that women with bipo-
lar disorder, regardless of treatment status, were at a higher
risk of instrumental birth, cesarean birth, and need for induc-
tion of labor than women without bipolar disorder (P ⬍ .001).
They found no significant differences in gestational diabetes,
an Apgar score less than 7, or neonatal hypoglycemia among
the 3 groups. A strength of this study was that it controlled
for smoking and substance use—behaviors that can indepen-
dently impact pregnancy outcomes.
Mei-Dan et al31 (N = 437,941) found that women with
bipolar disorder had a higher risk of giving birth to an infant
Journal of Midwifery & Women’s Health r www.jmwh.org
Additional records identified
through other sources
(n=5)
Records excluded
(n=158)
Full-text articles
excluded, with reasons
Case studies (n=9)
Integrated literature
reviews (n=3)
Articles included in
systematic reviews (n=6)
Low RAMSR score (n=1)
Low Newcastle-Ottawa
score (n=1)
Neurodevelopment
outcome (n=2)
who was large for gestational age (⬎ 97th percentile) than
women without mental illness (OR, 1.29; 95% CI, 1.08–1.54).
Unfortunately, there were no measures of other factors,
such as poor nutrition, smoking, or use of psychotropic
medications during pregnancy.
Nguyen et al30 (N = 3880) reviewed all pregnancies
associated with the diagnosis of bipolar disorder in the state
of California during a 3-year period. They found a higher
risk of preeclampsia (OR, 1.4; 95% CI, 1.1–1.6), preterm birth
(OR, 1.3; 95% CI, 1.1–1.3), birth weight below 2500 grams
(OR, 1.6; 95% CI, 1.4–1.8), infant death (OR, 2.7; 95% CI,
1.5–4.4), and gestational diabetes (OR, 1.8; 95% CI, 1.5–1.9)
in women with a diagnosis of bipolar disorder compared to
women without bipolar disorder. This study did not control
for confounding factors, such as substance use. It is likely
that many of the women included in this study were also on
psychotropic medications.
Jablensky et al20 (N = 1301) found that women with
bipolar disorder were more likely to have placenta previa
(OR, 2.13; 95% CI, 1.15–3.94) and antepartum hemorrhage
(OR, 1.60; 95% CI, 1.11–2.32) than women without mental
illness. They did not have data on smoking, illicit drug use
during pregnancy, maternal psychiatric morbidity, or use of
medications, so they could not control for these factors in
their analysis.
Overall, the large cohort studies20,29–31,34 and systematic
review15 demonstrate that women with bipolar disorder are
675
at increased risk of pregnancy complications, preterm birth,
and congenital abnormalities compared with women without
bipolar disorder. The data on large or small for gestational
age are difficult to interpret given that both were identified
in different studies. It is important to note that studies
varied in controlling for variables such as substance use and
psychotropic medications, which can influence pregnancy
outcomes.
Psychotropic Medications Used to Treat Bipolar
Disorder
Mood stabilizers are the first-line treatment for bipo-
lar disorder.35 Mood stabilizers include lithium and the
antiepileptic drugs valproic acid, lamotrigine, and carba-
mazepine (Tegretol). Atypical antipsychotics are also used to
augment mood stabilization in bipolar disorder. These drugs
include aripiprazole (Abilify), lurasidone (Latuda), olanzap-
ine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal),
and ziprasidone (Geodon). The physiologic changes of preg-
nancy, such as increased hepatic metabolism through the cy-
tochrome P450 enzyme system and increased renal clearance,
impact the drug levels of mood stabilizers and atypical an-
tipsychotics, requiring dose titrations during pregnancy.36,37
Table 1 lists the drugs approved by the US Food and Drug Ad-
ministration (FDA) for treating bipolar disorder, along with
common adverse effects and pregnancy-specific effects.
Mood Stabilizers and Impact on Pregnancy Outcomes
Lithium
Lithium is transported across the placenta and equilibrates
between the maternal and fetal circulation.21,38 Newport et
al21 compared outcomes in newborns exposed to high lithium
concentrations (⬎ 0.64 meq/L, n = 10) and newborns ex-
posed to low lithium concentrations (ࣘ 0.64 meq/L, n = 10)
in utero. All women were being treated for bipolar disorder. In
this study, 33% of the newborns exposed to high lithium con-
centrations were born at a premature gestational age, whereas
no newborns in the low-lithium-concentration group were
born prematurely (P ⬍ .05). The high-lithium-exposed group
had significantly lower mean one-minute Apgar scores (4.3 vs
7.0), more days in the hospital (10.1 vs 4.3 days), and more oc-
currences of low birth weight (40% vs 0%) compared with the
low-lithium-exposed group (P ⬍ .05). Forty-five percent of
the newborns with high lithium exposure had cardiovascular
complications (systolic murmur, cardiomegaly, and bradycar-
dia) compared with 18% of the newborns with low lithium
exposure. There were more neonatal complications in the
newborns with high lithium exposure than in the newborns
with low lithium exposure, with statistically significant dif-
ferences in central nervous system complications (lethargy),
neuromuscular complications (hypotonia, diminished deep
tendon reflexes, and poor suck or Moro reflex), and respira-
tory complications (apnea, cyanosis, labored breathing, and
need for intubation) (P ⬍ .05). Other neonatal complications
identified in this study were hepatic (hepatomegaly, jaundice),
renal (polyuria, diabetes insipidus), and thyroid (goiter).
676
Diav-Citrin et al22 followed 183 women who were treated
with lithium during pregnancy in Israel. More than 90%
were exposed in the first trimester, and 58.5% took lithium
throughout pregnancy. They compared rates of major anoma-
lies among 3 groups: 1) women who took lithium during
their pregnancy for multiple different psychiatric diagnoses;
2) women with bipolar disorder who were not treated with
medication (n = 72); and 3) women randomly selected from a
teratogenic information service who were counseled on expo-
sures to drugs that are known to be nonteratogenic (n = 748).
There was no significant difference in the incidence of in-
fants with major anomalies among the women in the groups.
When comparing cardiovascular anomalies with multicenter
data findings (Australia and Canada), they found that the in-
fants born to women in the lithium-exposure group had more
major anomalies (8.6%) and cardiovascular anomalies (3.9%)
than did the infants born to women who did not take lithium
during pregnancy (2.5% for women who used psychotropic
medications vs 0.5% in women who did not have lithium
exposure) (P ⬍ .01). McKnight et al’s16 systematic review
(N = 6 studies; 264 women) found that the odds of exposure
to lithium in cases of Ebstein’s anomaly did not significantly
differ from controls (OR, 0.27; 95% CI, 0.004–18.17). The au-
thors reported that the estimates calculated are unstable due
to the low number of Ebstein’s anomaly cases.
Diav-Citrin et al22 also reported on preterm birth and
pregnancy complications. The percentage of women who had
a preterm birth was higher in the lithium group compared
with the bipolar disorder group and the nonteratogenic
exposure group (13.7%, 10.2%, and 10.2%, respectively; P ⬍
.01). Women exposed to lithium during pregnancy also had
significantly higher percentages of miscarriages (16.4%) and
abortions (9.3%) than the women in the comparison groups.
Twenty-three percent of the women in the lithium-exposed
sample had pregnancy complications (gestational diabetes
mellitus, hypertension, oligohydramnios, toxemia, polyuria,
and polydipsia), and after exposure to lithium near term, 19%
had newborns with adverse outcomes (respiratory problems,
jaundice, tachycardia, tremor, sleepiness, and hypoglycemia).
The authors cautioned that their sample size was small,
resulting in the inability to detect rare outcomes.
In summary, infants exposed in utero to high serum
lithium concentrations are more likely to have cardiac anoma-
lies and neonatal complications than are infants exposed to
low serum concentrations of lithium. No studies in this re-
view controlled for confounders that could impact pregnancy
and neonatal outcomes, such as alcohol use and body mass in-
dex. In addition, one study22 reported that almost one-quarter
of women using lithium had pregnancy complications such as
gestational diabetes and hypertension, but other studies16,21
did not report on these complications, so no clear etiology has
yet been determined.
Antiepileptic Drugs
No studies were found that assessed the outcomes of women
diagnosed with bipolar disorder who were treated with
antiepileptic drugs. However, a large amount of data exists on
pregnancy outcomes in women with seizure disorders, and
many of the drugs used to treat seizure disorders are also
Volume 62, No. 6, November/December 2017
 Table 1. FDA-Approved Drugs Used to Treat Bipolar Disorder With Adverse Effects and Pregnancy-Specific Effects
Drug, Generic (Brand)
Mood stabilizers
Lithium (Lithobid)
Valproic acid
(Depakote)
Carbamazepine
(Tegretol)
Lamotrigine (Lamictal)
Atypical antipsychotics
Aripiprazole (Abilify)
Lurasidone (Latuda)
Olanzapine (Zyprexa)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Ziprasidone (Geodon)
Common Adverse
Approved Use Mechanism of Action Effects Pregnancy-Specific Effects
Acute manic episodes Possible inhibition of GI distress, polyuria, Increased drug elimination
Maintenance second messenger weight gain, sedation, lowers drug levels
enzymes ataxia, tremor
Acute and mixed mania Increases brain Sedation, tremor, Increased drug distribution
concentrations of GABA dizziness, ataxia, GI lowers plasma
distress, headache concentration
Acute and mixed mania Inhibits release of glutamate Sedation, dizziness, GI Increased CYP3A4 activity
Block voltage-sensitive distress, rash lowers drug levels
sodium channels in
neurons
Maintenance Inhibits release of glutamate Rash Increased phase 2
Binding to voltage-sensitive glucuronidation lowers
sodium channel in drug levels consistently
neurons throughout pregnancy
Acute mania/mixed Partial agonism at D2 and Dizziness, insomnia, Increased CYP2D6 activity
mania 5HT 1A receptors akathisia, activation, lowers drug levels
Maintenance nausea and vomiting,
weight gain (less risk)
Bipolar depression Blocks D2, 5HT 2A, and Sedation, akathisia, Increased CYP3A4 activity
5HT 7 receptors nausea lowers drug levels
Acute mania/mixed Blocks D2 and 5HT 2A Sedation, weight gain Decreased CYP1A2 activity
mania receptors (high risk) raises drug levels
Maintenance Antagonist at 5HT 2C
receptor
Acute mania Blocks D2 and 5HT 2A Dizziness, sedation, Increased CYP3A4 and
Maintenance receptors weight gain CYP2D6 activity lowers
Bipolar depression Agonism of 5HT 1A drug levels
Acute mania Blocks D2 and 5HT 2A Dose-dependent EPS, Increased CYP2D6 activity
Maintenance receptors hyperprolactinemia, lowers drug levels
Alpha-2 receptor antagonist weight gain, sedation
Acute mania/mixed Blocks D2 and 5HT 2A Anxiety, agitation, Increased CYP34A activity
mania receptors weight gain (less risk) lowers drug levels
Maintenance Agonism 5HT 2C and 1A
receptors

Abbreviations: CYP, cytochrome P450D2, dopamine 2; EPS, extrapyramidal symptoms; GABA, gamma-aminobutyric acid; GI, gastrointestinal; 5HT, serotonin.
Source: Sadock et al37

used to treat bipolar disorder, so those studies are included
in this review. Cunnington et al26 (N = 3416) analyzed data
from the International Lamotrigine Pregnancy Registry and
found no increase in major congenital malformations associ-
ated with increasing lamotrigine dose, but the authors noted
that the population was not large enough and could only de-
tect extremely large proportional increases of infants with spe-
cific types of malformations. Campbell et al25 also reported
no statistically significant increased odds of major congenital
malformations with increased doses of lamotrigine.
Gilboa et al’s33 meta-analysis (N = 7 studies) found
an increased risk for spina bifida after in utero exposure to
valproic acid (OR, 11.9; 95% CI, 4.0–21.2) and carbamazepine
(OR, 3.6; 95% CI, 1.1–4.5). An increased risk for cleft palate
was also seen in women who took valproic acid (OR, 5.8; 95%
CI, 3.3–9.5) and carbamazepine (OR, 2.4; 95% CI, 1.1–4.5)

Journal of Midwifery & Women’s Health r www.jmwh.org 677

during pregnancy. Campbell et al25 (N = 4975) reported
on data from the UK Epilepsy and Pregnancy Register. The
authors found statistically significant increases in major
congenital malformation rates with daily doses of valproate
and carbamazepine more than 1000 mg compared with doses
less than 1000 mg (P ⬍ .01). Valproic acid was associated
with a statistically significant higher percentage of neural
tube defects, facial clefts, cardiac anomalies, hypospadias,
gastrointestinal tract defects, genitourinary tract defects,
and skeletal anomalies compared with carbamazepine and
lamotrigine (P ⬍ .05). Folic acid supplementation had no
significant effect on major congenital malformations for
valproate, carbamazepine, or lamotrigine. Jentink et al11
reported increased odds of spina bifida (OR, 5.7; 95% CI,
2.6–12.3), cleft palate (OR, 3.0; 95% CI, 1.2–7.4), hypospa-
dias (OR, 6.7; 95% CI, 2.9–15.2), and atrial septal defect
(OR, 3.2; 95% CI, 1.5–7.0) when women took valproic acid
monotherapy compared with other antiepileptic drug (AED)
monotherapy (eg, carbamazepine, lamotrigine, phenobarbi-
tal). Jentink et al32 found that women taking carbamazepine
during pregnancy had a higher risk of infants with spina
bifida than women not taking carbamazepine (OR, 2.6; 95%
CI, 1.2–5.3). This study did not find any significant increased
risk for other malformations, such as cleft lip, diaphragmatic
hernia, or hypospadias, in the carbamazepine group.
Studies have found higher odds of major congenital mal-
formations, such as neural tube defects and cleft lip, with ex-
posure to valproic acid compared to in utero exposure to car-
bamazepine and lamotrigine. The daily total dose of valproic
acid and carbamazepine is an important factor in determining
the magnitude of major congenital abnormalities. Lamotrig-
ine has not shown this association. There were no studies in
this review on AED use in women with bipolar disorder, and it
has been suggested that epilepsy itself may impact pregnancy
outcomes independent of AEDs.33,39
Atypical Antipsychotics and Impact on Pregnancy
Outcomes
Antipsychotics have become more common for treatment
of bipolar disorder during pregnancy. This may in part be
because of concerns about an association between mood
stabilizers and congenital malformations. Use of atypical
antipsychotic medications during pregnancy has increased
from 6.3% in 2001 to 16.8% in 2007 in a US sample (N =
4223), with quetiapine prescribed most often.40
Three systematic reviews and 4 prospective cohort studies
were found that assessed the relationship between antipsy-
chotic use in pregnancy and pregnancy outcomes. Three
cohort studies23,27,28 did not find an association between
these drugs and an increased risk of major malformations,
whereas 2 meta-analyses17,19 did find an increased risk of
major malformations. Coughlin et al’s19 meta-analysis found
that the most common organ affected was the heart, but
there was no specific pattern of malformations found in
Terrana et al’s17 meta-analysis (Table 2). One study that
assessed the effects of individual antipsychotics based on
prescriptions written for a nationwide sample of pregnant
women enrolled in Medicaid (N = 1,360,101) found that
risperidone was associated with a small increased risk of
678
malformations overall (RR, 1.26; 95% CI, 1.02–1.56) and
cardiac malformations more specifically (RR, 1.26; 95% CI,
0.88–1.81) but found no increased risk associated with other
typical or atypical antipsychotics.28 The systematic review by
Ennis and Kamkier18 did not find that olanzapine, quetiapine,
risperidone, or aripiprazole was associated with an increased
incidence of congenital malformations.
With regard to preterm birth, one cohort study23 did not
identify any increased risk in women who took atypical an-
tipsychotics, and again in this instance, meta-analyses17,19 did
find a significant increased risk (Table 3). The cohort study
by Vigod et al23 used a high-density propensity score algo-
rithm to match medication users with nonusers for less bi-
ased estimates of treatment effects. This algorithm included
prescription drug claims and physician, hospital, and emer-
gency department diagnoses and services to address unob-
served confounders. They reported that when compared to an
unmatched cohort, women who took atypical antipsychotics
had a significantly higher risk of preterm birth, but this in-
creased risk was no longer present when the women were
compared to a matched cohort. In both meta-analyses,17,19 the
included studies did not control for substance use, medica-
tions, or psychiatric diagnoses, which may impact pregnancy
outcomes independently. The lack of control for confounding
factors in these studies might explain the difference in rates of
preterm birth that were found.
Kulkarni et al24 found in a sample of women with mixed
psychiatric diagnoses that newborns who experienced with-
drawal were exposed to high doses of antipsychotics at
12 weeks’ gestation compared to women who were on lower
doses of antipsychotics, but the effect was not statistically sig-
nificant. They did find that newborns exposed to high doses
of antipsychotics at 12 weeks’ gestation had a 13.4% increased
risk of being admitted to a neonatal intensive care unit (NICU)
compared with newborns exposed to lower doses of antipsy-
chotics. They found no statistical significant difference in
birth weight and respiratory distress at birth between infants
of women with psychosis and women with bipolar disorder.
In 2011, the FDA41 released a report stating that newborns
may experience withdrawal symptoms and abnormal muscle
movements (extrapyramidal signs) after in utero exposure
to antipsychotic medications during the third trimester. The
report includes typical antipsychotics (haloperidol [Haldol],
clozapine [Clozaril]) and atypical antipsychotics (risperidone,
quetiapine, aripiprazole, olanzapine). The FDA stated that a
majority of the cases were confounded by other psychotropic
medications and pregnancy complications independent of
antipsychotic medications. Given these findings and the FDA
recommendations, it is important to discuss with women
taking antipsychotics that neonatal withdrawal symptoms
may occur so that they can share decision making with their
mental health providers.
DISCUSSION
Women with bipolar disorder have risks of illness relapse
when maintenance medications are discontinued during
pregnancy. The disorder itself is associated with an in-
creased risk for preterm birth, congenital abnormalities, and
severely small for gestational age. Since most studies in this
Volume 62, No. 6, November/December 2017
 Table 2. Results of Included Studies and Systematic Reviews Reporting on an Association Between In Utero Exposure to Atypical Antipsychotics
and Major Malformations
Adjustment for
Author, Year, Country N Drugs Examined Confounders Result(s)
27 303 Aripiprazole, asenapine, Psychiatric medications,
Cohen et al No statistically significant increased risk
2016 clozapine, iloperidone, mental disorder of major congenital malformations (OR,
United States lurasidone, olanzapine, diagnosis and severity, 1.25; 95% CI, 0.13–12.19)
paliperidone, quetiapine, maternal age and BMI, 3 in exposed group vs one in unexposed
risperidone, ziprasidone planned pregnancy, group
substance use, prenatal Types of major congenital malformations
vitamins, white race listed: Transposition of great arteries,
VSD, imperforated hymen
23 41,523 SSRIs, mood stabilizers,
Vigod et al Quetiapine, olanzapine, No statistically significant increased risk
2015 risperidone benzodiazepines of major congenital malformations (OR,
Canada 1.19; 95% CI, 0.75–1.91)
44 in exposed group vs 40 in unexposed
group
No major congenital malformations listed
Huybrechts et al28 1,341,715 Olanzapine, quetiapine, Psychiatric and neurological No statistically significant increased risk
2016 risperidone, ziprasidone conditions, chronic of major congenital malformations (RR,
United States maternal illness, use of 1.05; 95% CI, 0.96–1.16)
other psychotropic 412 in exposed group vs 43,494 in
medications unexposed group
Increased risk of major congenital
malformations: Risperidone had a
slightly increased risk of overall
malformations (RR, 1.26; 95% CI,
1.02–1.56) and cardiac malformations
than the unexposed group
Coughlin et al19 1,577,861 Risperidone, quetiapine, N/A No statistically significant increased risk
2015 olanzapine, ziprasidone, of major congenital malformations (OR,
Sweden, Germany, paliperidone, clozapine, 1.39; 95% CI, 0.66–2.93)
Canada, United aripiprazole 131 in exposed group vs 48,466 in
Kingdom unexposed group
Increased risk of cardiovascular
malformations: (OR, 2.09; 95% CI,
1.50–2.91)
17 946,348 Aripiprazole, asenapine, N/A
Terrana et al Increased risk of major congenital
2015 clozapine, paliperidone, malformations (OR, 2.03; 95% CI,
Sweden, Germany, quetiapine, risperidone, 1.41–2.93)
Canada ziprasidone 51 in exposed group vs 30,741 in
unexposed group
Types of major congenital malformations
listed: CV, GI, MS, face, GU

Abbreviations: BMI, body mass index; CI, confidence interval; CV, cardiovascular; GI, gastrointestinal; GU, genitourinary; MS, musculoskeletal; OR, odds ratio; RR, relative
risk; SSRIs, selective serotonin reuptake inhibitors; VSD, ventricular septal defect.

Journal of Midwifery & Women’s Health r www.jmwh.org 679

 Table 3. Results of Included Studies and Systematic Reviews Reporting on an Association Between In Utero Exposure to Atypical Antipsychotics
and Preterm Birth
Adjustment for
Author, Year, Country N Drugs Examined Confounders Result(s)
23 41,512
Vigod et al Quetiapine, olanzapine, SSRI No statistically significant increased
2015 risperidone Mood stabilizer risk of preterm birth (RR, 0.85; 95%
Canada Benzodiazepines CI, 0.53–1.36)
39 in exposed group vs 44 in
unexposed group
Coughlin et al19 1,915,165 Risperidone, quetiapine, N/A Increased risk of preterm birth (OR,
2015 olanzapine, ziprasidone, 1.61; 95% CI, 1.15–2.25) 198 in
Sweden, Germany, paliperidone, clozapine, exposed group vs 77,070 in
Canada, United aripiprazole unexposed group
Kingdom
Terrana et al17 5422 Aripiprazole, asenapine, N/A Increased risk of preterm birth (OR,
2015 clozapine, paliperidone, 1.85; 95% CI, 1.20–2.86) 75 in
Sweden, Germany, quetiapine, risperidone, exposed group vs 362 in unexposed
Taiwan, Canada, ziprasidone group
United Kingdom,
Japan

Abbreviations: CI, confidence interval; OR, odds ratio; RR, relative risk; SSRIs, selective serotonin reuptake inhibitors.

review15,20,29,31 were conducted outside of the United States,
it is difficult to generalize their findings to pregnant women
who reside in the United States. Women who have an existing
mental illness are more likely to have concomitant substance
use disorders such as smoking,42 so lifestyle behaviors that in-
dependently affect perinatal outcomes may play a role in these
increased risks; a majority of the studies did not control for
these factors.
In this review, there were mixed psychiatric diagnoses in
the samples, polypharmacy confounders, and limited mea-
surements of outcomes in the studies. Lithium exposure can
increase the risk of preterm birth, cardiac malformations, and
neonatal complications, which may be dose related. Ebstein’s
anomaly was not found to be significant in these studies. This
abnormality occurs in the general population in one out of
20,000 births, and detecting a significant difference in the in-
cidence of this disorder following in utero exposure to lithium
would require a very large population size.
There is strong evidence that valproic acid is associated
with an increased risk for neural tube defects and other
malformations; therefore, it is contraindicated in preg-
nancy. Despite the recommendation to avoid valproic acid
during pregnancy, between 23.7% and 57.4% of valproic
acid prescriptions were given for affective disorders to
women of reproductive age (15–44 years) in the United
States, presenting concerns about neural tube defects in this
population.43,44
There are some data indicating a dose-related risk of mal-
formations with use of lamotrigine, and studies suggest that
carbamazepine is associated with an increased risk of neural
tube defects. The systematic reviews and meta-analyses
for AEDs were conducted with women who have epilepsy,
which may have an independent impact on pregnancy
outcomes. Finally, evidence is mixed with regard to atypical
antipsychotics’ effect on major congenital malformations and
preterm birth. Only one study28 found a small increased risk
with risperidone use for overall major malformations and
cardiac malformations. Studies with nonsignificant results
were conducted in the United States and Canada, while the
meta-analyses included only studies outside the United States.
These factors need to be considered in generalizing these find-
ings to childbearing women who reside in the United States.
In response to a call for clearer data presentation and rec-
ommendations for all medications, the FDA has eliminated
the pregnancy categories A, B, C, D, and X and implemented
the Pregnancy and Lactation Labeling Rule to include
pregnancy, lactation, and females and males of reproductive
potential, effective June 30, 2015. The Pregnancy category
includes the subsections risk summary, clinical considera-
tions, and data and information about pregnancy exposure
registries, if available. Drugs approved on or after June 30,
2001, are being phased in with the new labeling. This new
labeling assists health care providers in making educated
decisions with women about maintenance medication
use for bipolar disorder during pregnancy. Prenatal care
providers can review the labeling for updates on pregnancy
recommendations for bipolar disorder treatments.
Implications for Practice
When caring for women with bipolar disorder, a discussion
about the risks for relapse and adverse pregnancy outcomes
is an essential discussion during the process of shared deci-
sion making. The risks need to be put in context for individ-
ual women based on their past psychiatric history and previ-
ous pregnancies, if applicable. It is possible that having bipolar

680 Volume 62, No. 6, November/December 2017

disorder and perhaps associated substance use behaviors can
increase the risk of pregnancy complications such as placenta
previa and antepartum hemorrhage, as well as preterm birth
and major congenital malformations.
Psychotropic medications also need careful assessment.
Lithium and lamotrigine levels decrease due to the physiologic
changes of pregnancy, so women’s dosages need to increase
to maintain a therapeutic effect during pregnancy and de-
crease postpartum to avoid toxicity.45 Women taking lithium
may benefit from using an atypical antipsychotic in the third
trimester to avoid lithium toxicity.21
Women who take carbamazepine or valproic acid may
benefit from switching to another mood stabilizer such as
lamotrigine or atypical antipsychotic medications, if possible.
Ideally, women using one of these 2 AEDs should change
to a different medication before conception. Some women
may have a therapeutic response with only valproic acid or
carbamazepine and therefore may need to remain on one
of these medications during pregnancy. It is recommended
that women begin folate supplementation preconception
and during the first trimester for all AEDs to protect against
neural tube defects.46 Women taking carbamazepine or
valproic acid will need counseling about the risks and ben-
efits of these drugs and consultation with an obstetrician or
maternal-fetal-medicine specialist to establish a plan of care
for the pregnancy.
Although the studies of atypical antipsychotics have
mixed results with regard to preterm birth and major con-
genital malformations, they do have metabolic adverse ef-
fects that can contribute to high-risk pregnancies.47 To assess
for gestational diabetes, women using atypical antipsychotics
would benefit from glucose tolerance tests early in the second
trimester and repeated at 28 weeks’ gestation. There is a po-
tential for neonatal withdrawal symptoms and extrapyramidal
movements following in utero exposure to atypical antipsy-
chotics, and lower doses of these medications may improve
this risk. The avoidance of risperidone in the first trimester
may reduce malformation risks. It is important to explain to
women that stopping or switching psychotropic medications
in pregnancy may not remove the risk of fetal malformations
entirely.
If pregnant women make the decision to stop psy-
chotropic medications, they will benefit from stepwise
reductions to decrease withdrawal symptoms in collabo-
ration with their mental health care providers. If women
decide to discontinue lithium, gradual dose reductions
might decrease the frequency of mood relapses.48 These
women need close monitoring by their mental health care
providers during pregnancy and the postpartum period.
Nonpharmacologic treatments, such as psychotherapy and
social support for family members, are beneficial regardless
of women’s medication usage.17 Women who relapse with
manic and/or psychotic symptoms during pregnancy need
immediate referrals to the emergency department for their
safety.
Women with bipolar disorder are at risk for postpartum
psychosis. Doyle et al49 (N = 43) found a relapse rate of 46.5%.
The women who had a relapse were statistically significantly
younger (aged less than 31 years), more likely to have had an
unplanned pregnancy, and more likely to have had previous
Journal of Midwifery & Women’s Health r www.jmwh.org
postnatal episodes than women who did not have a postpar-
tum relapse. These women need a mental health plan before
giving birth. This plan includes the need for support and ad-
equate sleep.
Recent data on breast milk and psychotropic medica-
tions used to treat bipolar disorder demonstrate low relevant
infant dosages (below 10%) and low milk-to-plasma ratios
(below 1.0) with all mood stabilizers and atypical antipsy-
chotics, deeming them safe for breastfeeding women.50 Drugs
that have high protein bindings, such as valproate and car-
bamazepine, have the lowest milk-to-plasma ratios and may
meet the needs of breastfeeding women. Since combination
oral contraceptives lower valproate and lamotrigine levels,
women may need different birth control methods or higher
antiepileptic drug dosages to maintain mood stability.51
CONCLUSION
Concerns about psychotropic medication use during preg-
nancy are ongoing. It is important to discuss the current evi-
dence about pregnancy and bipolar disorder and the effects of
mood stabilizers and atypical antipsychotics and to recognize
that some women will need to continue a medication that may
be associated with increased risks to pregnancy or newborn
outcomes. Women with bipolar disorder need close monitor-
ing by their mental health care providers and may need addi-
tional consultation with a maternal-fetal medicine expert for
pregnancy care.
AUTHOR
Debra A. Scrandis, PhD, CRNP-F, CRNP-PMH, is an Asso-
ciate Professor at the University of Maryland Baltimore School
of Nursing and in clinical practice at Kraus Behavioral Health
in Catonsville, Maryland.
CONFLICT OF INTEREST
The author has no conflicts of interest to disclose.
ACKNOWLEDGMENTS
The author would like to thank Dr. Karen Scheu and
Dr. Charon Burda for their assistance with this article.
REFERENCES
1. daCosta SC, Passos IC, Lowri C, Soares JC, Kapczinski F. Refract-
ory bipolar disorder and neuroprogression. Prog Neuro-Psycho
pharmacol Biol Psychiatry. 2016;70:103-110.
2.Merikangas KR, Jin R, He J-P, Kessler RC, Lee S, Sampson NA, et al.
Prevalence and correlates of bipolar spectrum disorder in the world
mental health survey initiative. Arch Gen Psychiatry. 2011;68(3):241-
251.
3.American Psychiatric Association. Diagnostic and Statistical Man-
ual of Mental Disorders (DSM 5). 5th ed. Washington, DC: Author;
2013.
4.Passos IC, Mwangi B, Vieta E, Berk M, Kapczinski F. Areas of contro-
versy in neuroprogression in bipolar disorder. Acta Psychiatr Scand.
2016;134(2):91-103.
5.Frey BN, Dias RS. Sex hormones and biomarkers of neuroprotection
and neurodegeneration: Implications for female reproductive events in
bipolar disorder. Bipolar Disord. 2014;16:48-57.
681
 6.Viguera AC, Tondo L, Koukopoulos AE, et al. Episodes of mood disor-
ders in 2,252 pregnancies and postpartum periods. Am J Psychiatry.
2011;168:1179-1185.
7.Wesseloo R, Kamperman AM, Munk-Olsen T, Pop VJM, Kushner SA,
Bergink V. Risk of postpartum relapse in bipolar disorder and post-
partum psychosis: a systematic review and meta-analysis. Am J Psy-
chiatry. 2016;173:117-127.
8.Newport DJ, Stowe ZN, Viguera AC, et al. Lamotrigine in bipolar dis-
order: efficacy during pregnancy. Bipolar Disord. 2008;10:432-436.
9.Güveli BT, Rosti RO, Guzeltas A, Tuan EB, Atakl D, Sencer S. Ter-
atogenicity of antiepileptic drugs. Clin Psychopharmacol Neurosci.
2017;15(1):19-27.
10.Tomson T. Dose-dependent risk of malformations with antiepileptic
drugs: an analysis of data from the EURAP epilepsy and pregnancy
registry. Lancet Neurol. 2011;10(7):609-617.
11.Jentink J, Loane MA, Dolk H, et al. In utero valproic acid monother-
apy in pregnancy and major congenital malformations. N Engl J Med.
2010;362:2185-2193.
12.Cohen LS, Friedman JM, Jefferson JW, Johnson EM, Weiner ML.
A reevaluation of risk of in utero exposure to lithium. JAMA.
1994;271(2):146-150.
13.Kung J, Chiappelli F, Cajulis OO, Avezova R, Kossan G, Chew L, Maida
CA. From systematic reviews to clinical recommendations from ev-
idence based health care: validation of revised assessment of multi-
ple systematic reviews (R-AMSTAR) for grading of clinical relevance.
Open Dent J. 2010;4:84-91.
14.Wells GA, Shea B, O’Connor D, et al. The Newcastle-Ottawa scale
for assessing the quality of nonrandomized studies in meta-analyses.
http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
2010. Accessed January 25, 2017.
15.Rusner M, Berg M, Begley C. Bipolar disorder in pregnancy and child-
birth: a systematic review of outcomes. BMC Pregnancy Childbirth.
2016;16:331.
16.McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM,
Geddes JR. Lithium toxicity profile: a systematic review and meta-
analysis. Lancet. 2012;379:721-728.
17.Terrana N, Koren G, Pivovarov J, Etwel F, Nulman I. Pregnancy
outcomes following in utero exposure to second generation antipsy-
chotics: A systematic review and meta- analysis. J Clin Psychophar-
macol. 2015;35(5):559-565.
18.Ennis ZN, Kamkier P. Pregnancy exposure to olanzapine, quetiap-
ine, risperidone, aripiprazole and risk of congenital malformations:
a systematic review. Basic Clin Pharmacol Toxicol. 2015;116:315-
320.
19.Coughlin CG, Blackwell KA, Bartley C, Hay M, Yonkers K, Bloch M.
Obstetric and neonatal outcomes after antipsychotic medication expo-
sure in pregnancy. Obstet Gynecol. 2015;125(5):1224-1235.
20.Jablensky AV, Morgan V, Zubrick SR, Bower C, Yellachich L. Preg-
nancy, delivery and neonatal complications in a population cohort of
women with schizophrenia and major affective disorders. Am J Psy-
chiatry. 2005;162:1:79-91.
21.Newport, DJ, Viguera AC, Beach AJ, Ritchie, JC, Cohen LS, Stowe
ZN. Lithium placental passage and obstetrical outcome: implications
for clinical management during late pregnancy. Am J Psychiatry.
2005;162:2162-2170.
22.Diav-Citrin O, Shechtman S, Tahover E, Finkel-Pekarsky V, Arnon J,
Kennedy D, et al. Pregnancy outcome following in utero exposure to
lithium: a prospective, comparative observational study. Am J Psychi-
atry. 2014;171:785-794.
23.Vigod SN, Gomes T, Wilton AS, Taylor VH, Ray JG. Antipsychotic
drug use in pregnancy: high dimensional, propensity matched, popu-
lation based cohort study. BMJ. 2015;350:h2298.
24.Kulkarni J, Worsley R, Gilbert H, Gavrilidis E, Van Rheenen TE, Wang
W, et al. A prospective cohort study of antipsychotic medications in
pregnancy: the first 147 pregnancies and 100 one year old babies. PLoS
One. 2014;9(5):e94788.
25.Campbell E, Kennedy F, Russell A, et al. Malformation risks of
antiepileptic drug monotherapies in pregnancy: updated results from
682
the UK and Ireland Epilepsy and Pregnancy registries. J Neurol Neu-
rosurg Psychiatry. 2014,85:1029-1034.
26.Cunnington MC, Weil JG, Messenheimer JA, Ferber S, Yerby M, Tennis
P. Final results from 18 years of the International Lamotrigine Preg-
nancy Registry. Neurology. 2011;76(21):1817-1823.
27.Cohen LS, Viguera AC, McInerney, Freeman M, Sosinsky AZ,
Moustafa D, et al. Reproductive safety of second-generation antipsy-
chotics: current data from the Massachusetts General Hospital Na-
tional Pregnancy Registry for atypical antipsychotics. Am J Psychia-
try. 2016;173:263-270.
28.Huybrechts KF, Hernandez-Diaz S, Patomo E, Desal RJ, Mogun H, De-
jene SZ. Antipsychotic use in pregnancy and the risk for congenital
malformations. JAMA Psychiatry. 2016;73(9):938-946.
29.Boden R, Lundgren M, Brandt L, Reutfors J, Anderson M, Kieler H.
Women treated or not treated with mood stabilisers for bipolar disor-
der: population based cohort study. BMJ. 2012;345:e7085.
30.Nguyen N, Gorman M, Kent E, Caughey A. Pregnancy outcomes
in women with bipolar disorder: a retrospective cohort study. Am
J Obstet Gynecol. 2014;S323.
31.Mei-Dan E, Ray JG, Vigod SN. Perinatal outcomes among women
with bipolar disorder: a population based cohort study. Am J Obstet
Gynecol. 2015;212:367.
32.Jentink J, Dolk H, Loane MA, et al. Intrauterine exposure to carba-
mazepine and specific congenital malformations: systematic review
and case-control study. BMJ. 2010;341:c6581.
33.Gilboa SM, Broussard CS, Devine OJ, et al. Influencing clinical prac-
tice regarding the use of antiepileptic medications during pregnancy:
modeling the potential impact on the prevalence of spina bifida and
cleft palate in the United States. Am J Med Genet C Semin Med Genet.
2011;157:234-246.
34.Lee HC, Lin HC. Maternal bipolar disorder increased low birth weight
and preterm births: a nationwide population based study. J Affect
Disord. 2010;121(1-2):100-105.
35.Hirschfeld RMA, Bowden CL, Gitlin MJ, Keck PE, Suppes T, Thase
ME, et al. Practice Guidelines for the Treatment of Patients With
Bipolar Disorder. 2nd ed. Washington, DC: American Psychiatric As-
sociation, 2010.
36.Deligiannidis KM, Byatt N, Freeman MPM. Pharmacotherapy for
mood disorders in pregnancy: a review of pharmacokinetic changes
and clinical recommendations for therapeutic drug monitoring. J Clin
Psychopharmacol. 2014;34(2):244-255.
37.Sadock, BJ, Sadock VA, Sussan N. Kaplan & Sadock’s Pocket Hand-
book of Psychiatric Drug Treatment. 5th ed. Philadelphia, PA:
Wolters Kluwer; 2011.
38.Gonzales-Roderiguez A, Imaz ML, Guitart M, Torres A, Roda E,
Botet F, et al. Lithium during late pregnancy: pharmacokinetics and
neonatal outcomes. Eur Neuropsychopharmacol. 2013;23(S2):S390-
S390.
39.Galbally M, Roberts M, Buist A, Perinatal Psychotropic Review Group.
Mood stabilizers in pregnancy: a systematic review. Aust N Z J Psychi-
atry. 2010;44:967-977.
40.Toh S, Li Q, Cheetham C, et al. Prevalence and trends in the use of
antipsychotic medications during pregnancy in the U.S., 2001-2007:
a population-based study of 585,615 deliveries. Arch Womens Ment
Health. 2013;16:149-157.
41.US Food and Drug Administration. FDA Drug Safety Communica-
tion: Antipsychotic drug labels updated on use during pregnancy and
risk of abnormal muscle movements and withdrawal symptoms in
newborns. http://www.fda.gov/Drugs/DrugSafety/ucm243903.htm.
Published February 22, 2011.Accessed January 25, 2017.
42.Jackson JG, Diaz FJ, Lopez L, de Leon J. A combined analysis of world-
wide studies demonstrates an association between bipolar disorder and
tobacco smoking behaviors in adults. Bipolar Disord. 2015;17(6):575-
597.
43.Adedinsewo DA, Thurman DJ, Luo YH, Williamson RS, Odewole
OA, Oakley GP. Valproate prescriptions for nonepilepsy disorders
in reproductive age women. Birth Defects Res Part A. 2013;97:403-
408.
Volume 62, No. 6, November/December 2017
44.Wisner K, Leckman-Westin E, Finnerty M, Essock SM. Valproate pre-
scription prevalence among women of childbearing age. Psychiatr
Serv. 2011;62(2):218-220.
45.Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL. Lamotrigine
dosing for pregnant patients with bipolar disorder. Am J Psychiatry.
2013;170(11):1240-1247.
46.Hart Y. Management of women with epilepsy before and during preg-
nancy. Prog Neurol Psychiatry. 2008;12(3):6-8.
47.Boden R, Lundgren M, Brandt L, Reutfors J, Kieler H. Antipsychotics
during pregnancy: relation to fetal and maternal metabolic effects.
Arch Gen Psychiatry. 2012;69(7):715-721.
48.Viguera AC, Nonacs R, Cohen LS, Tondo L, Murray A, Baldessarini
RJ. Risk of recurrence of bipolar disorder in pregnant and non
pregnant women after discontinuing lithium maintenance. Am J Psy-
chiatry. 2000;157:179-184.
49.Doyle K, Heron J, Berrisford G, Whitemore J, Jones L, Wainscott G,
et al. The management of bipolar disorder in the perinatal period and
Journal of Midwifery & Women’s Health r www.jmwh.org
risk factors for postpartum relapse. Eur Psychiatry. 2012;27(8):563-
569.
50.Uguz F, Sharma V. Mood stabilizers during breastfeeding: a systematic
review of the recent literature. Bipolar Disord. 2016;18:325-333.
51.Herzog AF, Blum AS, Farian EL, et al. Valproate and lamotrigine
level variation with menstrual cycle phase and oral contraceptive use.
Neurol. 2009;72:911-914.
Continuing education units (CEUs) are available for this
article as a part of a continuing education theme issue. To
obtain CEUs online, please visit www.jmwhce.org. A CEU
form that can be mailed or faxed is available in the print
edition of this issue.
683