Sarah Yacobi, PhD, and Asher Ornoy, MD
Laboratory of Teratology, Department of Anatomy and Cell Biology, The Hebrew University Hadassah Medical
School, Jerusalem, Israel.
Abstract: Background: Lithium is a drug used mainly for the treatment of Bipolar Disorder (BD). Case reports and
several retrospective studies have demonstrated possible teratogenicity, but the data in the different studies was
inconclusive. Methods: We summarized all published studies in English, including case reports. Results: We found
24 case reports, of which six infants had congenital anomalies, five having cardiac anomalies, one of them being
Ebstein’s anomaly. In the retrospective studies there were, in the Lithium Baby Registry, 225 registered cases with
25 anomalies, 18 of them being cardiac, of which six had Ebstein’s anomaly. An additional retrospective study on
59 cases found seven anomalies, four of them being cardiac. On the other hand, none of the prospective studies
(296 liveborn infants) demonstrated any increase in the rate of congenital anomalies, although two had Ebstein’s
anomaly. All case control studies regarding Ebstein’s anomaly were negative, and among 222 infants with Ebstein’s
anomaly and 44 with tricuspid atresia none of the mothers had taken lithium during pregnancy. Conclusions:
Considering the serious limitations of the retrospective and case control studies that are also retrospective, lithium
does not seem to be a significant teratogen, and hence should be given, if indicated, in pregnancy. It is, however,
a possible alternative.
The teratogenicity of lithium following administra-
tion during the first trimester, or throughout preg-
nancy, has been demonstrated by several authors,
exhibiting high rates of cardiovascular defects, in
particular Ebstein’s anomaly.
Following these reports, the Lithium Baby Regis-
ter was founded in 1968 (1). Ever since, case reports,
case control, retrospective and prospective studies
have been performed, along with animal studies, in
order to evaluate the real embryotoxic effect of lith-
ium on the human embryo.
Lithium ions equilibrate across the placenta, and
therefore the concentrations in the maternal and
fetal plasma are almost equal. As a result, lithium in-
ported, the prevalent post-natal symptoms being:
low Apgar score, heart failure, hypotonicity and
nephrogenic diabetes insipidus (2).
In this review we survey and summarize all
human data published in the English literature and
draw conclusions regarding fetal effects of lithium
therapy during pregnancy. These conclusions could
lead to establishing a policy for both psychiatrists
and gynecologists while treating women with bipo-
lar disorders (BD) during pregnancy.
We reviewed all studies that discussed the
teratogenic and embryotoxic effect of Li intake dur-
ing pregnancy on infants born to mothers with BD.
For this purpose data were obtained from all pub-
lished studies and case reports in English, referenced
in Medline between the years 1969 and 2005 that in-
cluded the key words: lithium and pregnancy, with
related phrases such as lithium and embryotoxicity,
lithium and teratogenicity, lithium and Ebstein’s
anomaly, lithium, pregnancy and Ebstein’s anomaly
and lithium and cardiac anomalies. This review sur-
veys case report studies (including 24 separate cases)
between the years 1969–2005; retrospective studies;
Address for Correspondence: Asher Ornoy, MD, Laboratory of Teratology, Department of Anatomy and Cell Biology,
The Hebrew University Hadassah Medical School, Jerusalem, Israel. E-mail: firstname.lastname@example.org
We found 24 studies (3–26) each reporting one case.
Nine of these infants (one of which was stillborn)
were born to mothers with BD, who were treated
some time during pregnancy with lithium only. The
remaining 15 women were also treated with antide-
pressants and/or anti-psychotics or other drugs.
Pregnancy outcome: Generally, gestational age at
delivery was lower because of a higher rate of
prematurity (6/23) in liveborn infants. Birth weight
was higher in the eight infants born to mothers on
lithium monotherapy in comparison to the
polytherapy, with two being Large for Gestational
Age (LGA). In the polytherapy group there was only
one LGA infant (Table1a).
Perinatal toxicity: Lithium had the potential for
perinatal toxicity as reported in 78% (19/23) of the
liveborn infants (Table 1b). Most of these effects
were transitory and self limiting, lasting between
hours and a few weeks, partly because of the pro-
longed half life of the lithium in the newborn’s
serum. The complications included: goiter, respira-
tory distress, apnea, cyanosis and asphyxia,
cardiomegaly, A-V block, atrial flutter supra-ven-
tricular tachycardia, poor reflexes and hypotonicity.
In the polydrug therapy, similar complications were
observed, but the rate of goiter was higher (three
cases, of which one had also transient hypo-
thyroidism). Further subdivision of the complica-
tions is as follows (Table 1b).
Neuromuscular: The occurrence of cyanosis,
mother treated with lithium was first recorded by
Wilbanks et al. in 1970 (6). Although serum lithium
levels in the mothers were within normal limits,
those of the infants were much higher (2.4 and 2.2
mEq/L), dropping gradually within 13 days (27).
case reports (6, 8, 9, 11, 16, 21, 25, 28).
Neonatal goiter: Maternal lithium ingestion during
pregnancy is known to occasionally cause goiter in
the infants, as well as in the mother. We found four
cases of goiter from the 23 reported cases (10, 12, 15,
neonatal hypothyroidism. Neonatal goiter was
described in these infants in addition to other com-
plications such as respiratory, neurological and he-
Urinary — Polyhydramnios and nephrogenic dia-
betes insipidus (NDI): The most common side ef-
fect of lithium is polyuria, a form of NDI. Since
lithium crosses the placenta, Ang et al. (20) postu-
lated that fetal polyuria resulting in polyhydramnios
emerges by the same mechanism as the maternal.
polyhydramnios were reported (12, 14, 16, 20, 21)
and two cases of NDI (21, 24).
Relation between lithium blood levels and
perinatal complications: Four of the 23 reported
able findings on examination. Their serum Li levels
were 0.37, 0.57 0.9 and 1.0 mEq/L, within normal
therapeutic range. Both maternal and newborn’s
serum levels were similar (4, 5, 7, 18). The lithium
toxicity were, in several cases, below 1.0 mEq/L, but
in many it was much higher, the highest level being
46 mEq/L (29). In view of these results, it seems pos-
sible to link maternal and/or fetal blood Li levels
with postnatal complications.
anomalies; one of them was Ebstein’s anomaly and
the second patent ductus arteriosus (PDA). A third
case had delayed motor development (Table1c).
In the 15 cases of multi-drug therapy, there were
dextrocardia, PDA and Juxta ductal aortic
coarctation; another had PDA and the third
tricuspid regurgitation, which spontaneously re-
solved. Two had developmental delay. No Ebstein’s
anomaly was reported (Table1c).
Of the total 23 reported liveborn infants, only six
had congenital anomalies. Another three had devel-
opmental retardation while the others had various
complications of pregnancy. An additional case was
of a macerated stillborn infant. It is clear that there
was no specific pattern of anomalies, although most
(5/6) had cardiac anomalies.
Table 1a. The effect of in-utero exposure to lithium on birth weight and prematurity rate among infants born to women
with bipolar disorder in 23 * separate case reports
Gestational age (wks)**
Median birth weight gr
Term born / premature
(<36) / LGA
Lithium only3,3054 /
2,873 Lithium and other drugs
3,030 Both groups
* one additional stillborn infant from lithium was macerated and excluded.
**Mean ± SD
disorder — results of 23* separate case reports
in pregnancy /n
/cardiomeg. / A-V block
RDSApnea Cyanosis AsphyxiaSyst.
Goiter / Hepatomeg.
no. no.no. no. / NDI
Lithium only / 8
Lithium and other drugs /15
Both groups / 23
2 / 2
0 / 3
2 / 5
1 / 1
3 / 0
4 / 1
1 / 0
3 / 1**
4 / 1**
1 / 1
6 / 7
7 / 8
2 / 0
5 / 2
7 / 2
* one additional stillborn infant from lithium was macerated and excluded.
**One out of three mentioned
RDS — Respiratory distress syndrome
NDI — nephrogenic diabetes insipidus
Table 1c. The effect of in-utero exposure to lithium on malformations rate, developmental retardation, maternal lithium
levels and cord lithium levels among infants born to women with bipolar disorder — results of 23 separate case reports
Total no. /
Lithium only / 81010210.55–1.8
3 (1 year)
Lithium and other
Both groups / 23
a — one case had also dextrocardia and aortic coarctation; one malformation was skeletal: errors of segmentation of upper
n — number of live infants
Table 2. The effect of in-utero exposure to lithium on malformations rate, among 225 infants born to women with bipolar
disorder (of the Lithium Registry) (29)
no. of cases
(no.) / %
1880–41006 1234 10a/ 7b
CNS — central nervous system
Another two Down’s syndrome and one case of congenital toxoplasmosis were documented
a — number of postnatal death out of the 25 malformed infants
b — number of stillbirth out of 225 cases of lithium registry
/ no. of cases
Mean lithium intake
Gestational age ( week)
mean ± SD
birth weight / grams
mean ± SD
Term deliver. >36wk / 54984; 680; 726
(1st, 2nd, 3rd,tr.)
1270, 1090, 998
(1st, 2nd, 3rd,tr.)
34.2 ± 2.9
3490 ± 0.528
Premat.deliv. < 36 wks. / 302990 ± 0.78 a
* 84 complete maternal-infant records of 252 records from the international lithium register (1968–1983)
a — prematures compared to term infants p < 0.01
LGA — Large for gestational age
Although in the reported cases most anomalies
were of the cardiovascular system, we must keep in
mind that we do not know the number of the unre-
ported lithium-treated women with normal chil-
In a retrospective study published in its final form in
1980, including all 225 cases of the registry,
Weinstein (29) reported 25 malformed infants from
a total of 225 reported lithium babies (11.1%). This
rate consisted of 18 (8%) cardiovascular defects —
six of which were Ebstein’s anomaly. The other seven
formed infants died during the first postnatal week
(Table 2). In addition to the 25 malformed infants,
there were seven stillborn infants, two children had
Down syndrome and one had congenital
toxoplasmosis. This registry was published partly in
several other studies, by Weinstein and Goldfield
(30), Weinstein (1, 31), and by Schou et al. (28).
Troyer et al. (32) reviewed the records of these
225 infants from the International Registry of Lith-
ium Babies and found 84 complete maternal-infant
data that included gestational age at delivery and
pregnancy increased the incidence of premature
birth, as over one-third (35.7%) were prematurely
born. They also demonstrated more than two-fold
increase in large for gestational age infants (LGA)
among prematures compared to the term born in-
fants (37% vs15.0%, Table 3).
From a total of 350 infants born to manic-depressive
women, information was obtained by Kallen and
Tandberg (33) for 287 cases (82%). In this group, a
sub-group of 59 infants exposed to either lithium
alone or lithium in combination with other psycho-
and to 38 women treated with antidepressants other
than lithium. In the 59 Li-exposed group, a 10.2%
neonatal death rate was reported, as well as a 11.9%
malformation rate (seven infants) and 6.8% (four in-
of anomalies among the lithium-treated newborns
was higher as compared to control untreated manic-
depressive women, the difference was not statisti-
cally significant and, due to the small sample size,
could still be random. Ebstein’s anomaly was not
Nested case-control study: Kallen (34) evaluated all
infants with cardiac defects born to 716 women hos-
pitalized for BD and compared two matched con-
trols for each malformed infant. Fourteen cardiac
defects were identified, more than twice the ex-
pected rate. One infant had a chromosomal anomaly
had Ventricular Septal Defect and two had a systolic
murmur — all considered to be relatively mild car-
diac anomalies. The others had other cardiac anom-
alies, including one case of Ebstein’s anomaly that
was not exposed in utero to lithium or other antide-
pressants. There was no significant difference in the
rate of exposure to lithium between the malformed
(3/13) and the control infants (4/20). Thus, lithium
could not be associated with the increase in the rate
of cardiac anomalies. One possible explanation for
the lack of this association, given by the author, was
nancy was diagnosed.
Retrospective case control study: Czeizel and Racz
lies between the years 1980–1987. Their study in-
cluded all malformed still-born and live-born cases
diagnosed from birth till the age of one year, as well
as prenatally diagnosed and electively terminated
malformed fetuses. They observed no association
with maternal lithium use during pregnancy; how-
ever, only six infants were exposed to lithium.
In a joint case-control study Kallen (36) collected
25 cases of Ebstein’s anomaly and 44 cases of
tricuspid atresia. In addition, he added 15 cases of
Ebstein’s anomaly that were reported in France.
None of these infants with Ebstein’s anomaly or with
tricuspid atresia were exposed in-utero to lithium
Sipek (37) reported 89 cases of infants with
Ebstein’s anomaly in a Czech study, conducted be-
tween 1960–1985. None of their mothers were
treated with lithium during pregnancy. The author,
however, could not rule out possible occupational
exposure to lithium. No statistical differences were
found in exposure to lithium between these mothers
anomalies (7.1% vs. 11.4%).
Table 4. The effect of treatment with lithium taken by 59 women with bipolar disorder on neonatal death and malforma-
tion rate — a retrospective cohort study (33)
no. / %
Total no. of infants
no. / %
no. / %
no. / %
B-D untreated women190382 2**
0 Psychotrophic drugs — not lithium38
Lithium ± other psychotr. drugs 594 4*
* out of the four malformed infants: three died and one with transposition of great vessels survived the neonatal period
**one infant also had Down syndrome
Table 5. The link between lithium therapy during pregnancy and the rate of Ebstein’s anomaly among infants of women
with B–D performed by four different researchers and analyzed by Cohen et al. (44)
Authorsyear Lithium Exposure among
tricuspid atresiaEbstein’s InfantsControl
Zalzstein et al.
Edmonds & Oakley
Total no.of cases
0 / 40
0 / 89
0 / 59
0 / 34
0 / 222
0 / 44
0 / 44
0 / 138
0 / 178
1 / 168
0 / 34
1 / 518
Zalzstein et al. (38) analyzed data from 59 pa-
tients diagnosed as having Ebstein’s anomaly, using
168 children with neuroblastoma as a control group.
They found that none of the mothers of the 59 chil-
dren had lithium therapy during pregnancy. These
results led them to the conclusion that lithium does
not increase the rate of cardiac anomalies, especially
of Ebstein’s anomaly.
In a case-control study, Edmonds and Oakley
(39) compared 76 infants who were “possibly” born
with Ebstein’s anomaly with the same number of
control infants. Of the 76 infants, 34 were confirmed
as Ebstein’s anomaly. However, none of them or of
the control group were born to women with BD or
were exposed to Li during pregnancy.
Ebstein’s anomaly is defined as downward displace-
ment and malformation of the tricuspid valve, often
together with atrial septal defect (ASD) and right
ventricular hypoplasia. The basal risk rate of
Ebstein’s anomaly is about 1:20,000 live births in the
during the first trimester of pregnancy, the risk for
Ebstein’s anomaly apparently mounts to 1:1,500
births. The cardiac teratogenic effects of early expo-
sure to lithium had been proven to be less ominous
than originally thought (41–43).
Confirmation for the doubts as to the possible
link between lithium and the rare Ebstein’s anomaly
came from two studies summarizing data regarding
lithium exposure during pregnancy and Ebstein’s
case-control studies mentioned above (36–39) None
to be exposed to lithium during pregnancy, whereas
two children of the 398 controls were exposed to
lithium in-utero. Following this analysis, the risk for
Ebstein’s anomaly, estimated by Cohen et al. (44)
ranged between 0.1% (1:1000) and 0.05% (1:2000)
births. The risk of other cardiovascular defects
among infants born to mothers who consumed lith-
ium in pregnancy ranged between 0.9% (similar to
controls) in prospective studies to 12% in retrospec-
al. (45) who analyzed 180 cases of Ebstein’s anoma-
lies from the same case-control studies and found
that none of the malformed infants was exposed in
utero to lithium. Kallen (34) supposed that, in spite
of all the results that link Li-therapy during preg-
nancy to high rates of severe cardio-vascular malfor-
mation, there is a possibility that the psychiatric
disease itself or genetic dispositions for the disease
may link lithium and consequent cardiac malforma-
tions. Therefore, in order to verify or disprove the
real correlation between Li-therapy in pregnancy
and teratogenicity, much larger prospective studies
should be performed. The results of an American
Expert Scientific Committee on lithium in preg-
nancy were published by Moore in 1995 (46).
In summary: While two retrospective studies show
a significant association between Li intake by the
pregnant mother and cardiac anomalies and one did
not, the studies mentioned above regarding 222
cases of Ebstein’s anomaly and 44 cases of other car-
diac anomalies are entirely negative. Thus, if a corre-
lation between in utero lithium exposure and
Ebstein’s anomaly exists, it is weak.
We found only one record linkage study and two
published prospective studies regarding lithium use
in pregnancy, and they were all negative regarding
In a record linkage study of Michigan Medicaid
by Briggs et al. (48), only two (3.2 %) of 62 infants of
women treated with lithium during the first trimes-
ter of pregnancy were reported to have major con-
genital anomalies, and none of them was cardiac.
In an uncontrolled prospective study Cunniff et
al. (49) identified 72 lithium-treated women with
BD. Of these, six had pregnancy termination, four
12 were lost to follow-up. Only 50 were known as
live-born infants, two of them reported as having
major malformations: one lumbar myelo-
meningocele and the other unilateral inguinal her-
generally observed in controls. There were no cases
of cardiac anomalies.
In another controlled prospective study, Jacob-
son et al. (50) studied the pregnancy outcome of 138
Li-exposed pregnant women (who gave birth to 105
liveborn infants), and 148 controls. They observed
one case of Ebstein’s anomaly, but failed to show any
differences with respect to major congenital anoma-
lies and number of livebirths between controls and
lithium exposed group (Table 6).
In the lithium-exposed group, four malforma-
tions were observed: two neural tube defects, one of
which was exposed also to carbamazepine. The third
infant had meromelia and died because of
prematurity, and one fetus was diagnosed as severe
Ebstein’s anomaly at 16 week gestation and preg-
anomalies observed were: ventricular septal defect
(VSD); congenital hip dislocation (CDH) and cere-
bral palsy (CP) with torticolis. Birth weight was
higher in the lithium group (Table 6).
In the controlled prospective study from our
Israeli Teratogen Information Service, yet
105 pregnant women exposed in pregnancy to
lithium (86% were exposed from the first trimester),
79 liveborn infants. Two infants were malformed
(2.9%). One infant had cryptorchidism that was
operated and the other had Ebstein’s anomaly. This
was compared to 1,234 control infants with 39 cases
of major malformations (3.2%), none of which had
Ebstein’s anomaly. In addition, there was an 8.7%
rate of pregnancy interruptions (vs. 2.9 in the
controls) and 14.3% of spontaneous abortions (vs.
5.9% in the controls).
Table 6. The effect of lithium therapy given to women with B-D on pregnancy outcome and malformation rate among their infants — a controlled
prospective study (50)
no. of cases
mean / range
age* / range
Types of malformations
/ 6 (4%)
/ 15 (10%)
3 (3%) 1. meningomyelocele, hydrocephalus
(treated: Li + carbamazepine
2.spina bifida + tethered cord
3. meromelia,born& died 23wk,1/twins
1 severe form of Ebstein's anomaly
diagnosed wk.16, pregnan. terminated
/ 7 (5%)
/ 9 (6%)
3 (2%) 1. Ventricular septal defect
2 Congenital hip dislocation
3. Cerebral palsy & torticolis
Four sets of twins were born in the Li group: one pair died from complications of prematurity at 23 weeks.
One set of twins was born in the control group.
* Mean ± SD
** significantly higher than controls
was unknown) with 296 liveborn infants, there were
eight malformed (2.7%), not different from controls.
However, two of the malformed infants had Ebstein’s
anomaly while none of the 43 malformed infants
among 1,354 controls (3.2%) had this cardiac anom-
A sample size of 296 liveborn infants exposed to
lithium with a ratio of 1:4.6 (lithium/control) and a
power of 80%, assuming a baseline risk of 3% for
major anomalies, enables detection of a 2.27-fold in-
crease in the overall rate of major anomalies (with
It is interesting that only few perinatal complica-
tions were described in the retrospective or prospec-
tive studies, apparently due to the fact that this was
not the main purpose of these investigations.
While experimental studies in animals have shown
long-term developmental effects of psychotropic
drugs, including altered emotional behavior in adult
mice exposed in-utero to fluoxetine (52), most de-
velopmental studies in children exposed in-utero to
such drugs are negative (53). Several human case re-
ports have demonstrated transient neuro-
developmental deficits in infants born to lithium
exposed mothers (26). However, long-term develop-
mental studies on lithium-exposed children are gen-
erally lacking. In a single prospective follow-up
study, Schou (54) compared the motor and mental
their own 57 siblings, who were not exposed to lith-
ium in-utero. The data were calculated based on the
information obtained from questionnaires and let-
ters sent to doctors (psychiatrists/general practitio-
ners) who primarily reported the children. Out of 60
lithium-exposed children, 10 were abnormally de-
veloped, in six developmental delay was transitory
three children were exposed to lithium only in the
nancy. In the 57 control siblings, six children were
identified with persistent abnormal development.
The data shown by Schou indicates that in-utero ex-
posure to lithium does not increase the risk of devel-
opmental (both motor and mental) disorders.
pregnancy by women with BD on their offspring,
with special emphasis on major anomalies. Con-
cerns about the correlation between lithium and se-
vere congenital cardiac defects encouraged
spective studies (29, 33) described a total number of
284 infants born to mothers with BD who took lith-
ium in pregnancy, of them 22 (7.7%) had cardiac
anomalies, six (2.1%) having Ebstein’s anomaly.
These studies demonstrated high rates of cardiovas-
cular malformations, notably Ebstein’s anomaly.
Since these reports were voluntary, it was only
natural that over-reporting of malformed infants
would be expected, as is the main weakness of most
retrospective studies. Hence, several prospective
trolled) were negative. Similarly, all case control
studies regarding cardiac anomalies also failed to
show an association between in-utero lithium expo-
sure and cardiac anomalies, including Ebstein’s
Table 7. The effect of in-utero exposure to lithium on psychomotor development among infants born to women with bipo-
lar disorders (54)
Treatment Group Duration / treatmentNormal develop. Abnormal develop. Age of children*Male / female
Lithium 60 20 — 1st tri.
40 — entire pregnancy
50 10 7.3 ± 0.2
12.2 ± 0.8
26 / 34
Control Siblings 57516 25 / 32
* Mean +SD
The strong impact of the high rate of cardiac
anomalies from the lithium registry seems to stem
from the fact that the same cases were published in
was completed, and it was not always clear from the
publications that they refer to the same cases. Kallen
results, although not statistically significant, point to
the same possibility of increased cardiac anomalies
in association with lithium therapy in pregnancy.
were six infants with major congenital anomalies
and three with developmental delay. Of the mal-
formed infants, five had cardiovascular defects, one
of them had Ebstein’s anomaly. As high as it may be
seen, these results do not reflect the real malforma-
tion rate, since we do not know how many women
took lithium without having malformed infants. It is
also clear that there is no specific pattern of anoma-
lies following lithium intake, except for, possibly,
Reviewing the data accumulated until today re-
garding lithium exposure and cardiovascular anom-
alies, including Ebstein’s anomaly, it is to be
concluded that the risk is much lower than previ-
ously thought, and that whenever lithium is given to
pregnant women with BD, treatment should con-
tinue. It is however advisable to perform a fetal
echocardiography to exclude the possibility of car-
Warner (40) suggested that the real impact of
lithium is under-represented since many women
who become pregnant while being treated with lith-
ium may prefer to abort the malformed fetuses. In-
deed, Jacobson et al. (50) reported a higher rate
(though not statistically significant) of therapeutic
abortions in the lithium exposed group (10%) com-
pared to 6% in the control. This was also corrobo-
rated in our findings: 8.6% in the lithium group vs.
2.9% in the controls (51).
Since not all women with BD can be stabilized
with lithium, a comparably safe alternative is
needed. Other mood stabilizers such as
carbamazepine and valproic acid, used for the same
indications in BD patients, are certainly more
teratogenic and, whenever possible, should be re-
placed by lithium. An apparently effective and rela-
tively safe alternative in pregnancy seems to be
sible effects of lamotrigine in pregnancy was initi-
ated by the manufacturer: GlaxoSmithKline,
from the international registry reported with first
trimester monotherapy of lamotrigine, they found
dose-related effect was detected in daily doses lower
than 400 mg, while the regular daily doses are about
200 mg. Most of the cases in this registry were re-
cently published by Cunnington et al (56).
Another recent prospective study of the U.K. epi-
lepsy and pregnancy register (57) reported 647 cases
of exposure to lamotrigine monotherapy during
pregnancy. Of these, 21 infants (3.2%) demonstrated
major congenital anomalies, compared to 6.2%
major anomalies found among 715 valproate-ex-
posed infants. Daily lamotrigine doses above 200
mg. induced higher risk of anomalies, as 15 mal-
formed infants (5.4%) were reported from 279 such
exposures. No studies were found regarding the
long-term developmental effects of lamotrigine in
pregnancy on the offspring. Hence, lamotrigine can
women with BD.
In a retrospective study, Viguera et al. (58) studied
the recurrence rate of bipolar disorders following
disruption of lithium treatment among pregnant
women as compared to non-pregnant women. No
differences were found between the groups during
the first 40 weeks (52% and 58% appropriately), yet
these rates were over two fold the recurrence rate of
bipolar disorders of both groups in the precedent
year (21%) (58).
These findings suggest a limited protective effect
of pregnancy itself in regards to risk of BD recur-
rences and brought Viguera et al. (43) to the conclu-
sion that of all the mood stabilizers, lithium should
mood stabilizers are yet limited.
Evaluation of the studies on lithium in pregnancy
shows that lithium therapy throughout pregnancy
does not seem to increase the general rate of major
anomalies, and apparently adds only a small risk for
cardiovascular defects, notably Ebstein’s anomaly.
is the drug of choice in women with BD, it may be
continued even in pregnancy. Moreover, it is advis-
able not to discontinue lithium in pregnancy as it
may subsequently lead to relapse of the disorder.
This is in spite of the fact that treatment of BD pa-
tients with lamotrigine was recently proven quite ef-
fective, and that prospective studies regarding its use
in pregnancy are so far reassuring. In addition, preg-
nancy of lithium-treated women should be consid-
ered high risk, and therefore monitoring during
pregnancy has to include fetal echocardiography,
Pregnancy interruption in lithium-treated mothers
can probably be considered only if a severe cardiac
(or other) anomaly is diagnosed.
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