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risperidone, olanzapine, and quetiapine. These researchers used a voluntary reporting database in Japan for this study. The relative risk for spontaneous miscarriage
was found to be signicantly greater for women taking aripiprazole than for unexposed women; this signicant difference was not present for other second-generation antipsychotics: ROR 2.76 (CI 1.62–4.69). Of the 18 women reporting
miscarriage with aripiprazole, 12 had a diagnosis of schizophrenia, treated with a
median dose of aripiprazole 12mg. This nding has been discussed elsewhere in the
literature; Cuomo etal. (2017) mention the miscarriage signal for aripiprazole use
in pregnancy reported by these Japanese researchers, but also mention other studies
which do not support an increase in the rate of congenital malformations or of miscarriage for women taking aripiprazole (Huybrechts et al. 2016; Habermann
etal. 2013).
By contrast with research by Sakai etal. (2017), Bellet etal. (2015) conducted a
review of 86 cases of babies exposed to aripiprazole in pregnancy excluding all
exposures to known teratogens, including other psychotropic medications, in the
rst trimester. This team drew cases from a reporting service available in France for
monitoring adverse outcomes, and screened for substance use, smoking, and other
lifestyle factors in the women identied. Women with pre-existing diabetes were
excluded. Pregnancy outcomes included a high rate of elective termination (9.3%),
consistent with other studies, and a miscarriage rate within the general population
rate (again, 9.3%).
C. Breadon and J. Kulkarni
8.10.4 Clozapine andRisk ofStillbirth or Miscarriage
inPregnancy
Mendhekar etal. (2003) report on a stillbirth associated with monotherapy of clozapine 75mg throughout pregnancy, including the rst trimester. Aside from case
reports, there is very little information about stillbirth, miscarriage, or ectopic pregnancy rates in babies exposed to clozapine in pregnancy.
8.11 Premature Infants/Low Birth Weight Infants
8.11.1 Schizophrenia andPremature Birth/Low Birth Weight:
Another Instance ofPotential Confounding by Indication
Looking primarily at diagnosis rather than treatment modality and examining
women treated prior to the era of widespread use of atypical antipsychotics,
Jablensky etal. (2005) noted a slight trend to preterm birth, a lower mean birth
weight, reduced head circumference and reduced length in babies of women with
schizophrenia. There was a suggestion in this study that babies of women with
schizophrenia experienced intrauterine growth restriction after adjustment for ethnicity, maternal age, infant gender, plural birth, and marital status. This group also
adjusted for the expected impact of smoking (extrapolated from other studies; this
8 Antipsychotics inPregnancy
201
data set did not include smoking rates) and found an additional residual effect of
schizophrenia diagnosis alone (or the presence of an unaccounted-for additional
moderator). This study could be considered a proxy for examining treatment using
rst-generation antipsychotic agents, as it studied a population of women diagnosed
(and presumably treated) in the 1980s.
Consistent with these earlier results, Vigod etal. (2014) found a much higher rate
of preterm birth in the babies of women with schizophrenia regardless of treatment
modality, with rates of 11.2% compared with 6.2% in the control group. Adjusted
odds ratio was 1.75 (CI 1.46–2.08). Women with schizophrenia were also statistically more likely to deliver very preterm infants (<32weeks). Similarly, the women
in Reis and Kallen’s 2008 cohort taking antipsychotics for mental health reasons
were signicantly more likely to have babies born before 37weeks, with an odds
ratio of 1.73 (95% CI 1.31–2.29). Matevosyan (2011) found rates of premature
labour in women with schizophrenia which the author considered high (5.1% RR
1.98), but which remained well within statistical norms. This author did nd a statistical increase in rates of babies with growth retardation born to mothers with
schizophrenia (RR 2.16, CI 1.48–3.87). These ndings were echoed by Hizkiyahu
etal. (2009), who found that babies born to women with a diagnosis of schizophrenia were signicantly more likely to be of low birth weight (13.4% vs. 7.8%,
p=0.042). Later research by Vigod etal. (2020) also found a higher rate of preterm
birth (aRR 1.64 (CI 1.51–1.77) and small for gestational age babies (aRR 1.40, CI
1.20–1.64) in babies of women with schizophrenia. Similarly, Fabre etal. (2021) in
their recent study found increased rates of intra-uterine growth retardation at aOR
1.37 (1.17–1.59), small for gestational age (aOR 1.34, CI 1.19–1.50) and preterm
birth (aOR 1.64, CI 1.42–1.90) in babies of women with a diagnosis of schizophrenia.
8.11.2 Women withSchizophrenia andLow Birth Weight Babies
Born at Term
Vigod etal. (2014) found a correlation between diagnosis of schizophrenia in the
mother and small for gestational age infants, though these researchers did not stratify according to treatment. The unadjusted odds ratio for small for gestational age
babies (<third centile) born to women with schizophrenia was 1.56 (95% CI
1.25–1.95). Reis and Kallen (2008) found that women taking antipsychotics for
mental health reasons were also signicantly more likely to have babies born at low
birth weight (<2500g): OR 1.67 (95%CI 1.21–2.29). Jablensky etal. (2005) found
a signicant increase in low birth weight infants born to mothers with schizophrenia, regardless of the timing of onset of their illness (whether prior to or after the
birth). This approach seemed to account well for any effect associated with
treatment.
Lin et al. (2010) found that women with diagnoses of bipolar disorder and
schizophrenia were more likely than women without a mental illness to have babies
of low birth weight, even after adjustment for sociodemographic and metabolic factors. These babies were also more likely to be small for gestational age.
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C. Breadon and J. Kulkarni
8.11.3 Bipolar Disorder andPremature Birth/Low Birth
Weight Infants
Lin etal. (2010) found that women with bipolar disorder were more likely than relatively demographically matched controls to have preterm babies (OR 2.08 CI
1.53–2.83). In support of this view, Lee and Lin (2012) cite MacCabe etal. (2007)
in suggesting that mothers with mood disorders have elevated risk of preterm birth
and small for gestational age babies. Both treated and untreated women with bipolar
disorder studied by Boden etal. (2012a, b) had similarly increased rates of preterm
birth, further supporting the view that perhaps this risk may not relate to medication
treatment, but instead to other factors underlying the diagnosis or associated
sociodemographic risks.
8.11.4 Women withBipolar Disorder andLow Birth Weight
Babies Born at Term
In the 2012 study by Boden et al., women with bipolar disorder who remained
untreated were much more likely to have babies of low birth weight at delivery.
Interestingly, this study examined head circumference, which alone of weight,
length, and head circumference remained signicant after adjustment for confounders in women with untreated bipolar disorder. These researchers suggested that
maternal psychosocial stress in pregnancy in the context of untreated bipolar disorder may be the mechanism responsible, or that women with bipolar disorder were
more vulnerable to adverse neonatal outcomes such as low birth weight because of
associated demographic and lifestyle factors. These researchers also drew an association between small for gestational age infants and neonatal hypoglycaemia,
which could be associated primarily with the condition of small-for-gestational-age
itself rather than with the administration of psychotropic medications.
8.11.5 Typical Antipsychotic Medications andPrematurity/Low
Birth Weight
There appears to be a consensus relating to the correlation between typical antipsychotic exposure and preterm birth in most early studies, and this is borne out in
recent work as well. The study by Munk etal. (2005) suffered from low numbers in
the target population, but did nd a trend towards risk of preterm birth and low birth
weight in women taking rst-generation antipsychotics throughout pregnancy.
Diav-Citrin etal. (2005) found that gestational age at delivery was lower in a
cohort of women taking haloperidol for multiple different diagnostic indications, as
was median birth weight. Babies exposed to haloperidol in pregnancy were 2 times
more likely to be born prior to 37weeks. When the data were analysed for the relative strength of predictors of low birth weight, only haloperidol and smoking were
signicant predictors.
8 Antipsychotics inPregnancy
203
8.11.6 Typical Antipsychotic Medications andLow Birth Weight
Babies Born at Term
Habermann etal. (2013) found that babies of women taking rst-generation antipsychotics had the lowest birth weights when compared with babies of women taking second-generation antipsychotics or those unexposed, but that the difference in
birth weights was not clinically signicant, especially when preterm babies were
excluded from this analysis: these researchers found median weight at delivery of
3.38 kg for rst-generation-exposed babies compared with 3.4 kg for secondgeneration- exposed babies, and 3.44 kg for unexposed babies. Diav-Citrin etal.
(2005) noted that their group of term infants exposed to haloperidol in utero was
lighter by 165g than the reference cohort. Overall, Newham etal. (2008) found in
a small sample that babies exposed to typical antipsychotics weighed signicantly
less than babies exposed to atypical antipsychotics than a reference group of unexposed babies (p<0.05).
8.11.7 Atypical Antipsychotics andPrematurity/Low Birth Weight
Infants exposed to second-generation antipsychotics in the study by Sadowski etal.
(2013) were approximately 2.5 times more vulnerable to prematurity compared
with controls (10.6% vs. 4.3%). There was also a marked difference between gestational age of neonates exposed to one second-generation antipsychotic in comparison with those exposed to polypharmacy (p=0.005). Similarly, unmatched cohorts
in the study by Vigod etal. (2015) showed a higher rate of preterm birth in women
taking atypical antipsychotic medication in pregnancy, at 14.8% vs. 10.3%.
However, there was not a signicant increase in low birth weight even in the
unmatched cohort in this study. Boden’s group of women taking only antipsychotic
medication demonstrated higher rates of preterm birth when comparing medications other than olanzapine and clozapine with unexposed groups. McKenna etal.
(2005) found a trend to prematurity in women treated with atypical antipsychotics
(13% vs. unexposed 8%) but this difference was not signicant. 10% of exposed
babies were of low birth weight, vs. 2% of comparators; this difference was signicant (p=0.05).
Wichman (2009), conducting a retrospective review of birthing records for a
tertiary referral maternity centre, found 16 women prescribed atypical antipsychotics in pregnancy. These women predominantly had diagnoses of major depressive
disorder (44%), schizoaffective disorder, or bipolar disorder, and over half were
prescribed quetiapine. There is no data on concomitant medications, which are
likely to have been prescribed given the diagnostic categories treated. The average
age at delivery was 37weeks and 5days, with 18.75% of babies born prematurely.
Comparison data were not available in this study to evaluate signicance. Average
birth weight was low, at 3188g.
Terrana etal. (2015) conducted a meta-analysis of cohort studies examining second-generation antipsychotics. This group found that these babies were
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C. Breadon and J. Kulkarni
signicantly more at risk of preterm birth (OR =1.85 (1.20–2.86), though this
impact was decreased under a xed effects model (OR=1.51, CI 1.15–1.98) and
further decreased with adjustment (aOR= 1.34, CI 0.85–2.11) to lose statistical
signicance. This meta-analysis did not nd a signicant increase in the risk for
small-for-gestational age or large-for-gestational age babies, respectively, though
noting that the studies evaluating large for gestational age babies were not
homogeneous.
Hence the data is more mixed in relation to the risk of low birth weight in babies
exposed to atypical antipsychotics in pregnancy, though the trend to mild prematurity seems in most studies to remain.
8.11.8 Atypical Antipsychotics andLow Birth Weight Babies
Born at Term
Sadowski etal. (2013) did not nd a signicant difference in the incidence of babies
who were small for gestational age at delivery between women exposed to secondgeneration antipsychotics and those unexposed. This group also did not nd any
signicant difference in birth weight. Examining antipsychotic medication exposure in pregnancy, Boden et al. (2012a, b) found a much higher unadjusted risk
(more than double) of small for gestational age babies than the general population,
regardless of the type of antipsychotic medication to which they were exposed.
However, signicance disappeared once maternal factors were adjusted for.
McKenna etal. (2005) found 10% of exposed babies had a low birth weight, compared with 2% of unexposed babies. This difference was not statistically
signicant.
A meta-analysis by Coughlin etal. (2015) presented some complexity when considering birth weight. Including both typical and atypical antipsychotic medications
in this analysis led to a slight reduction in the birth weight of babies born to treated
mothers, but the mean difference was small: 57.9g. This analysis showed a relationship between antipsychotic exposure of all kinds and small for gestational age
infants, but not for large for gestational age infants, again not separating the effects
of typical and atypical agents. This analysis noted that heterogeneity between studies existed in relation to reporting of smoking status, obesity, alcohol use, illicit drug
use, socioeconomic status, confounding by indication or concomitant medication
use, all of which are known to affect all parameters studied. Virtually none of the
studies reported doses, which could also affect the risk to the exposed foetus.
Interestingly, these authors took issue with the “typical/atypical” division commonly used in analysing antipsychotic medications, noting that both groups include
a diversity of medications which can have different risks associated with their use.
These authors advocated drug-specic data reporting, to help clarify the true risk
presented by each medication.
8 Antipsychotics inPregnancy
205
The study by Bellet etal. (2015) found a signicant increase in the rate of preterm birth (16.4%, OR 2.57, CI 1.06–6.27) in babies exposed to aripiprazole. There
was also a signicantly increased rate of foetal growth retardation in the exposed
group (OR 2.97, CI 1.23–7.16). There was a slightly reduced mean weight in
exposed neonates compared with their peers (3268g compared with 3339g).
8.11.9 Studies Comparing First- (Typical) andSecond-Generation
(Atypical) Antipsychotics andtheRisk ofPrematurity
Petersen etal. (2016a, b) found that babies of women taking typical antipsychotics
in pregnancy appeared at higher risk of prematurity or low birth weight (11.8%)
than those taking atypical antipsychotics in pregnancy (8.4%), and much higher risk
than those never exposed to antipsychotic medication (3.9%). Habermann etal.
(2013) found those exposed to rst-generation antipsychotics had higher rates of
premature birth (15.7%) than either women taking second-generation antipsychotics (9.2%) or those unexposed to any antipsychotic in pregnancy (8.7%), and that
this difference was statistically signicant (OR 1.96 rst-generation antipsychotic
vs. unexposed cohort, 95% CI 1.29–2.98), also citing similar results in Lin etal.
(2010). One confounding variable raised by Habermann’s group was the very high
rate of concurrent antidepressant use in the cohort treated with rst-generation antipsychotics, which could also have an effect on preterm birth.
The 2015 meta-analysis by Coughlin et al. showed a statistically signicant
increase in rates of preterm birth of babies exposed to both typical and atypical
antipsychotics in utero, but these studies were heterogeneous. It seemed that the
impact of antipsychotic exposure in pregnancy on gestational age at delivery was
present, but small, leading to babies born a mean of 0.21weeks earlier.
In passing (as their focus was on weight at term birth), Newham etal. (2008)
excluded from their sample 16% of infants exposed to typical antipsychotics and
17% exposed to atypical antipsychotics, who were delivered prematurely. Of this
group, 21.4% of patients taking olanzapine had preterm deliveries (compared with
no patients taking haloperidol or risperidone). They compared this group with a
reference group of unexposed infants, of whom 2% were premature and 5% were
post-dates. This result contrasts with the study by Brunner etal. (2013) using the Eli
Lilly reporting database on olanzapine, which found rates of premature birth of
9.8% in these babies compared with a population rate of 12.8%.
Kulkarni etal. (2014) did not stratify their results according to antipsychotic
class, noting that a large majority of their cohort took atypical antipsychotics.
Interestingly, these authors stratied by dose, and found that dose of antipsychotic
(measured in risperidone equivalents) correlated inversely with prematurity. Babies
born at term were exposed in the rst trimester to an average of 2.6mg risperidone
equivalent dose, whereas babies born prematurely were exposed to an average of
5.0mg, p=0.02.
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C. Breadon and J. Kulkarni
8.12 Second-Generation Antipsychotics andHigh Birth
Weight Infants
8.12.1 The Influence ofaDiagnosis ofMental
Illness: Schizophrenia
Vigod etal. (2014) did not sub-categorise women’s treatment medication, but considered all women with a diagnosis of schizophrenia together. In this cohort they
found that 4.5% of babies born to women with schizophrenia were born at larger
than the 97th centile, compared with 2.7% in the referent group. This comparison
was adjusted for maternal age, parity, income, community size, pre-existing diabetes, hypertension, thromboembolic disease, and infant gender. The adjusted odds
ratio for this was 1.53 (CI 1.17–1.99).
8.12.2 Second-Generation Antipsychotics andHigh Birth
Weight Infants
The same group subsequently more closely examined the nexus between treatment
of mental illness in pregnancy and large for gestational age babies (Vigod et al.
2015). Focusing on atypical antipsychotic use, this study showed an increase in high
birth weight (>97th centile) babies born to the cohort treated with atypical antipsychotics compared with the unmatched general population. However, when matched
for health service usage and demographics, this outcome was no longer signicantly
different in the treatment group, suggesting that lifestyle risks associated with a
diagnosis of mental illness could also be responsible for the discrepancy.
Habermann etal. (2013) did not nd a signicant increase in birth weight of
babies exposed to second-generation antipsychotics in utero in comparison with
controls. Similarly, Reis and Kallen (2008), observing a cohort of women taking
both rst- and second—generation antipsychotics for their mental health, did not
nd a signicant increase in rates of high birth weight.
Boden etal. (2012a, b) did not separately examine the effect of antipsychotics on
birth weight. However, treatment of women with bipolar disorder with mood stabilisers including antipsychotics resulted in a non-statistically signicant increase in
the risk of large for gestational age infants. The authors’ hypothesis, that macrocephaly might relate to specic medications (olanzapine and clozapine) seemed to
be borne out in the results of the second study undertaken by this group, in women
taking antipsychotic medication. The most striking nding was that this group of
infants had an adjusted OR of 3.02 (1.60–5.71) for head circumference more than 2
standard deviations from the average. This was such an unusual nding that the
authors assessed for the possibility that hydrocephalus might account for the difference, which it did not.
Sadowski etal. (2013
antipsychotics in pregnancy were more likely to be large for gestational age (>90th
centile), at p<0.05. However, after analysing for treatment effect, this group felt
) found that babies born to women taking second- generation
8 Antipsychotics inPregnancy
207
that the major predictor of large for gestational age babies was pre-pregnancy
weight of the mother. Notably, this does not discount the effect of second- generation
antipsychotics on this outcome, but suggests that the impact may occur prior to
conception.
Interestingly, in contrast to most other published data, Newport et al. (2007)
performed a placental transfer study showing that only haloperidol was associated
with high birth weight babies (>4000g) in 15.4% of patients, whereas olanzapine,
risperidone, and quetiapine were not correlated with this outcome. This outcome
was noted in a study with low total number of 51 women.
The blockbuster study in this area is Newham etal. (2008) with results that, if
replicated, have signicant implications for medication choices in treating
women with multiple risks for obesity in pregnancy. Newham etal. (2008) note
that, aside from the putative effect of atypical antipsychotic medication, risk factors for macrosomia at delivery are maternal obesity, type I diabetes, gestational
diabetes and excess pregnancy weight gain. This group focused on gestational
weight at term delivery, excluding all women with a diagnosis of diabetes, those
whose babies had congenital malformations, or who were taking both a typical
and atypical antipsychotic medication. Large and small for gestational age were
dened as below the tenth or above the 90th centile. Newham etal. (2008) found
a highly signicant increased rate of large for gestational age infants in the group
exposed to atypical antipsychotics (20%) than in both the typical antipsychotics
(2%) or the reference unexposed group (3%), p<0.05. This difference was even
more marked when the babies exposed to olanzapine and clozapine were compared with the reference group. Of these babies, 31% were large for gestational
age. Notably, this study did not record maternal smoking or alcohol use, which
they considered a limitation. These authors also considered a cohort effect on
infant size over time, as rates of obesity in women have increased over that
time period.
They further note that large for gestational age infants can cause their own complications at delivery for the mother including vaginal lacerations, postpartum
haemorrhage, and increased risk of emergency caesarean section. Risks for the baby
cited by Newham etal. (2008) include birth trauma, shoulder dystocia and foetal
hypoxia, as well as risks for higher BMI and greater incidence of diabetes in
later life.
8.13 Neonatal Distress andAdverse Neonatal Events
8.13.1 Definitions
There is a plurality of names for the cluster of signs and symptoms that may manifest when placental transfer of a substance and its metabolites comes to an abrupt
end at delivery. Habermann etal. (2013) note the difculty in comparing rates of
neonatal distress due to the absence of an internationally agreed measure or scale
for these events.
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C. Breadon and J. Kulkarni
Convertino etal. (2016) hypothesise that this cluster may represent either the
residual toxic effects of a substance which is no longer efciently metabolised by
infant kidneys and liver, or alternatively a withdrawal from a high blood level of a
substance which is no longer available. These authors suggest that in the case of
antipsychotics, some symptoms occur as a consequence of cholinergic rebound, and
others relate to dopamine blockade. The multiple names for this syndrome include
“neonatal abstinence syndrome”, “neonatal withdrawal syndrome”, “neonatal adaptation syndrome”, or “neonatal behavioural syndrome” and in the case of antipsychotics, encompass a range of symptoms and signs including agitation, feeding
disorders, abnormalities of tone, respiratory distress, somnolence, and tremors
(Vigod etal. 2015). They can appear within hours after delivery, and some reports
suggest that they can remain up to a month afterwards (Vigod etal. 2015).
8.13.2 The Influence ofDiagnosis ofMental Illness onAdverse
Events at Delivery
Reis and Kallen (2008) found increased rates of low APGAR scores, respiratory
diagnoses and hypoglycaemia in the babies of women treated with antipsychotics
for mental illness, but none of these differences reached signicance. These scores
were adjusted for maternal age, parity, smoking, and history of prior miscarriage.
Vigod etal. (2020) also found low APGAR scores in babies of women with a diagnosis of schizophrenia, APGAR <8 at 1min (aRR 1.49, CI 1.40–1.59) and APGAR
<8 at 5min (aRR 1.90 CI 1.68–2.16).
Babies whose mothers had either treated or untreated bipolar diagnoses (Boden
etal. 2012a, b) had a diverse APGAR range, which was difcult to interpret. Babies
whose mothers were not treated seemed more at risk of low APGAR though this
difference did not reach signicance; babies whose mothers were treated with medication did not seem to be as much at risk of low APGAR as the general population.
Boden etal. (2012a, b) also examined the risk of neonatal hypoglycaemia; both
treated and untreated populations were more highly at risk for this outcome, though
this risk only reached signicance in the untreated cohort.
Jablensky etal. (2005), focusing on risks relating to underlying maternal diagnoses of psychiatric illness, noted that there was a trend towards lower APGAR score
at 5min, respiratory depression and intubation in babies of women with schizophrenia. Matevosyan (2011) echoed this outcome, nding a statistical increase in rates
of low APGAR scores at 5min for babies of mothers with schizophrenia.
Vigod etal. (2014) found a highly elevated risk of neonatal abstinence syndrome
for babies of mothers with schizophrenia (aOR=53.7, 95%CI=36.8–78.4). In this
research, neonatal abstinence syndrome is classied separately from Respiratory
Distress Syndrome, which these authors also found more commonly in babies of
mothers with schizophrenia (aOR=1.86, 95%CI =1.23–2.81), as were seizures
(aOR = 4.21, 95%CI = 2.31–7.65), intraventricular haemorrhage (aOR =2.43,
95%CI = 1.34–4.41), and persistent foetal circulation (aOR = 3.19,
95%CI=1.43–7.14).
8 Antipsychotics inPregnancy
The fascinating coda to this alarming warning was that, on re-examining the data
and matching with controls with similar patterns of healthcare utilisation (Vigod
etal. 2015), these differences became less marked. When these data were also controlled for the use of psychotropics other than antipsychotic medications, in particular antidepressants, mood stabilisers,and benzodiazepines, these outcomes lost
signicance. Regardless, the authors argue that these women and their babies are
still at much higher risk of adverse outcomes than the general population, and hence
should be observed and supported much more closely. It seems, however, on the
basis of this analysis, that it is not necessary to avoid the use of antipsychotics for
these women, which should help maintain mental stability throughout pregnancy
and beyond.
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8.13.3 First-Generation Antipsychotics andAdverse
Neonatal Events
There has been awareness of the possibility of withdrawal syndromes and extrapyramidal side effects from antipsychotic use in pregnancy for many years (Falterman
and Richardson 1980, via Petersen etal. 2016a, b). More recently, both the United
States’ Food and Drug Administration and the United Kingdom’s Medicines and
Healthcare Products Regulatory Agency updated their advice on risks of extrapyramidal effects and withdrawal syndromes in 2011in regard to typical antipsychotic medication use in pregnancy. Advice from the US FDA was based on 69
cases reported between 2008 and 2011. Symptoms included agitation, hypertonia,
hypotonia, tremor, somnolence, respiratory distress, and feeding disorder.
Einarsson and Boskovic (2009), completing an exhaustive review of all known
studies relating to antipsychotics in pregnancy, found a paper from 1971 which
described neonatal withdrawal and extrapyramidal symptoms in babies exposed to
higher doses of chlorpromazine, up to several weeks after birth (Farkas etal. 1971).
These authors note other reports of extrapyramidal side effects after exposure to
typical antipsychotics which persisted up to months after delivery (O’Connor etal.
1981), and two reports of paralytic ileus in neonates after exposure to typical anti-
psychotics (Falterman etal. 1980).
8.13.4 Adverse Events Associated withFirst- andSecond-
Generation Antipsychotics: Is This aUseful Distinction
inAssessing Risk forNeonates?
Convertino etal. (2016) note that both rst-generation and second-generation antipsychotic use in later pregnancy have been associated with increased rates of abnormal neuromotor performance, hypertonicity, and tremors. These authors mention in
this context the 2011 USFDA warning, mentioned above. Convertino etal. (2016)
also mentioned results from Kulkarni et al. (2014) in the Australian National
Register of Antipsychotic Medications in Pregnancy (NRAMP) of rates of medical