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Table 12.1
A.BDZs with medium-long plasma half-life
Drug name
Pro-nordiazepam-like BDZs: Prazepam, clobazam, desmetil-diazepam, urazepam,
Nitro-BZDs: Nitrazepam, unitrazepam
Pharmacokinetic features
Plasma half-life: More than 24 (24–100hours) including active metabolites with long
Metabolism: Demethylation to nordiazepam, hydroxylation, and conjugation by glucuronic
Interactions: SSRIs, oral contraceptives, can decrease hepatic hydroxylation and increase
plasma levels of these BZDs. Sedative effect hypotension when combined with alcohol or
CNS depressant drugs.
B.BZDs with short/ultra-short plasma half-life
Drug name: Alprazolam, bromazepam, brotizolam, estazolam, triazolam
Pharmacokinetic features
(a) Plasma half-life: 2–6h for triazolam, brotizolam, lormetazepam; 12–24h for other
(b) Metabolism: Hydroxylation and conjugation with glucuronic acid; no production of
Interactions: SSRIs and oral contraceptives can inhibit hepatic hydroxylation and can increase
Plasma levels of these BDZs
Sedative effects and hypotension when combined with alcohol or CNS depressant drugs
C.BZDs with short/ultrashort plasma half-life
Drug name: Oxazepam-like BZDs: Camazepam, lorazepam, lormetazepam, oxazepam,
temazepam)
Pharmacokinetic features
(a) Plasma half-life: 12–24h
(b) Metabolism: Conjugation with glucuronic acid; no production of active metabolites
Interactions: No relevant pharmacokinetic drug interactions. Sedative effect and hypotension
when combined with alcohol or CNS depressant drugs
Pharmacokinetic, metabolic pathways, interactions of BDZs
chlordiazepoxide, diazepam, ketazolam, medazepam, pinazepam, quazepam
half-life
acid
BZDs
active metabolites
effective anxiolytic and/or hypnotic dose. This is particularly important during the
gestational period to avoid/minimize a neonatal withdrawal reaction after delivery.
12.3 Use ofBDZs andZ-Drugs inPregnancy
Pregnancy is a period of physical and psychological changes, to the extent that some
women have difculties in handling their mixed feelings of happiness and fear or
concern for their future life. Epidemiological studies have documented that most
psychopathological conditions may arise or worsen during the gestational period,
which may require timely drug treatment and/or psychotherapy and social support.
Consequently, it is important not to underestimate the occurrence of prodromal
symptoms like tension, sadness, emotional distress, irritability, and sleep difculties
affecting a pregnant woman, as these symptoms could represent predictive warning
signs of a psychiatric disorder.
12 Benzodiazepines andZ-Drugs inPregnancy
293
Anxiety disorders and insomnia are frequently reported during pregnancy, with
prevalence rates which varies widely according to different epidemiological studies.
These psychopathological conditions can be moderate but persistent and, in many
pregnant women, can lead to relevant levels of distress and impairment of their
quality of life. It is well known that both severe anxiety disorders and persistent
insomnia can occur in comorbidity with major depressive disorders or other psychopathological conditions (Goodman etal. 2014; Okun etal. 2015).
Psychiatric disorders during pregnancy and postpartum are common, and about
15% of women experience peripartum depressive disorders frequently associated
with severe anxiety and sleep difculties. Drug utilization studies are needed to better understand not only the rate and trend of anxiolytic and hypnotic drug prescriptions during pregnancy and post-partum but also their pattern of use, i.e., dosage,
length of treatment, drugs used in association, and the diagnostic indication that
made the prescription necessary.
Recently, a meta-analysis of 32 studies coming from 28 country and including
more than 7 million of pregnancies conrmed that BDZ and Z-drugs use before,
during, and after pregnancy is prevalent. The worldwide prevalence of prescriptions
of these drugs during pregnancy was 1.9%; the highest prevalence rate was found in
the third trimester (3.1%); lorazepam was the most frequently prescribed drug
among BDZs.
Given the substantial proportion of newborns exposed in utero to BDZ and
Z-drugs, future research should continue to study their safety prole during the
perinatal period. Moreover, it would be desirable that the prescription of such medications should always be shared with the patient and her partner in order to explain
the potential risk of an untreated psychopathological condition as well as the risks
and benets of the drug treatment (Betcher and Wisner 2020).
12.4 Risk ofCongenital Major Malformations
12.4.1 Benzodiazepines
The fetal safety of BDZs during pregnancy was investigated since the rst publications
which date back more than 20years ago. In a meta-analysis, including 3 cohort and 6
case-control studies, BDZs as a class were considered at risk of major congenital malformations, particularly concerning some birth defects such as cleft lip and/or cleft palate (oral cleft) (Dolovich et al. 1998). As well, even an overview including studies
published from 1966 to 2000 conrmed such teratogenic risk for the BDZs advising
against its use in early pregnancy (Iqbal etal. 2002). A meta-analysis of 9 cohort studies,
with over 1 million of analysed pregnancies, including about 4500 newborns exposed in
utero, reported some years later different results documenting that BDZs do not carry
any risk of increase of major malformations in women exposed in the rst trimester of
pregnancy (Enato etal. 2011). Recent investigations, systematic reviews, and metanalytic studies indicate that the prescription of BZDs in the rst trimester of pregnancy
should not be considered contraindicated anymore, even though in clinical practice their
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utilization always needs a careful risk/benet assessment and regular clinical monitoring of the patient undergoing treatment.
A large cohort study conducted in the UK on about 2000 pregnant women
exposed to BDZs in the rst trimester reported reassuring results about their risk of
teratogenicity. Overall, the prevalence of malformations was 2.7% in 1159 children
of mothers prescribed diazepam, 2.9% in 379 children with temazepam, 2.5% in
406 children with zopiclone, and 2.7% in 19,193 children whose mothers had diagnosed depression and/or anxiety but were not exposed to BDZs. When compared
with 2.7% in 351,785 children with no diagnosed depression/anxiety nor medication use, the adjusted odds ratios were 1.02 (99% CI. 0.63–1.64) for diazepam, 1.07
(CI, 0.49–2.37) for temazepam, 0.96 (CI, 0.42–2.20) for zopiclone and 1.27 (CI,
0.43–3.75) for other anxiolytic/hypnotic drugs and 1.01 (CI, 0.90–1.14) for unmedicated depression/anxiety. These ndings clearly conrm that the risks of system-specic birth defects were generally similar in children exposed and not
exposed to anxiolytic and hypnotic drugs considered in the study, The authors’ conclusions were that no evidence of increased risk of malformations, associated with
antenatal drug exposure to diazepam, temazepam, zopiclone and other anxiolytic/
hypnotic drugs, were found in their study. These data strongly support that the exposure to BDZs and Z-drugs during early pregnancy may be considered safe as far as
the risk of major malformations is concerned (Ban etal. 2014).
A meta-analysis of 8 cohort studies evaluated the risk of major malformations in
neonates of 5195 exposed women to BDZs vs more than 2 million unexposed
women. BDZs were not associated with a statistically signicant risk of malformations in 8 studies or cardiac malformations in 4 studies. However, it was found a
statistically signicant relative risk of malformations only when BDZs were associated with an antidepressant drug (Grigoriadis etal. 2019).
These results, however, have been questioned from a methodological point of view in
a recent paper by Andrade, whose conclusions suggest that “gestational exposure to
BDZs is a marker of risk for major and cardiac malformations and importantly, that rst
trimester exposure to BDZs may not be associated with much increase in risk, if at all”
(Andrade 2019a). More recently in a nationwide cohort study of approximately 3 million
pregnancies conducted in South Korea, rst- trimester BDZ use was associated with a
modest increase in risk of malformations, particularly concerning heart defects. The risk
of primary outcomes increased with a higher mean daily dose of BDZs (more than
2.5 mg/day of lorazepam-equivalent dose), suggesting a dose–response relationship.
Although the risks were similar between short- and long-acting BDZs, a small but statistically signicant increase in relative risk (RR, 1.08 to 2.43) was found with some specic
agents including midazolam, diazepam, unitrazepam, and chlordiazepoxide (Noh etal.
2022). Although the relative risk found in this study was small, the potential low risks
should be always evaluated against the efcacy of BDZs in many patients and above all,
that BDZs must be prescribed in each patient using the “lowest effective dosage”, particularly in early pregnancy as, according to such study, the risk might be dose-dependent.
It should be noted, however, that so far this is the only study in which a dose-dependent risk of malformation in newborns exposed to BDZs in pregnancy has been found.
It is reasonable to conclude from most of data published and according to most the best
original studies, overviews and recent guidelines, that fetal exposure of BDZs and
12 Benzodiazepines andZ-Drugs inPregnancy
295
Z-drugs during rst trimester of pregnancy, at therapeutic dosages, should be considered
safe, at least in terms of risk of major congenital birth defects (McAllister-Williams etal.
2017; Bellantuono etal. 2013). Recently, a large population-based cohort study con-
ducted in Taiwan using data from a national database has not conrmed the risk of
malformations associated with BDZ and antidepressant drugs exposure in early pregnancy (Chuang etal. 2024). This study included 2. 634,021 singleton pregnancies, and
8599 patients (0.3%) were concomitant users of antidepressants and BDZs during the
rst trimester. The results did not identify an increased relative risk for overall malformations, heart defects, or any of the other organ-specic birth defects, except for digestive system malformations. In terms of absolute risk (AR), the rate of overall
malformations was 3.81 per 100 pregnancies with exposure, as compared with an AR of
2.87 per 100 pregnancies without drug exposure. The lack of an increased risk for overall malformations associated with concomitant use of antidepressants and BDZs was
also supported by the analyses controlling for confounding by indication and siblingmatched comparisons.
12.4.2 Z-Drugs
The information on the fetal and neonatal safety of the Z-drugs has been so far quite
scarce. Only for zolpidem there are few studies focusing on its use in early pregnancy. A rst prospective study carried out on 45 pregnant women who used zolpidem in comparison with a group of untreated pregnant women did not report any
congenital malformation in 90 newborns exposed in utero, including 17 who were
exposed during the rst trimester of pregnancy (Juric etal. 2009). As well a cohort
study did not nd a statistically signicant difference in rates of major malformations between a group of pregnant women who were treated during early pregnancy
with zolpidem and an untreated control group (Wang etal. 2010).
A recent study including a small sample of pregnant women, including 84 cases
exposed to zolpidem and 46 controls, was conducted using data from two multi-site
case-control studies. Seven defects had sufcient sample size to calculate adjusted
odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four
defects had odds ratios > 1.8; all condence intervals included the null. The authors’
conclusions were that the results do not support a large increase in risk, but smaller
increases in risk for certain birth defects cannot be ruled out as the sample of patients
was small (Howley etal. 2024). Data from the Swedish Medical Birth Registry from
1995 up to 2007 were used to identify 1318 women who reported the use of HBRAs
in early pregnancy. They gave birth to 1340 infants. Maternal characteristics and the
presence of congenital malformations were compared with all other women who
gave birth (n=1,106,001) and all other infants (n =1,125,734) born during the
study period. The probability of using HBRAs increased in women who had had 3
or more earlier miscarriages or 5 or more years of involuntary childlessness. An
excess use of other drugs and above all psychoactive drugs was seen in women
reporting use of HBRAs. The authors’ conclusions were that maternal use of
HBRAs in early pregnancy does not seem to increase the risk of major congenital
malformations (Wikner and Källén 2011). In the above-mentioned study by Ban
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which compared the safety of anxiolytic and hypnotic drugs during rst trimester of
pregnancy, a rate of 2.5% of newborns with major malformation was reported in
406 cases exposed to zopiclone, as compared to a rate of 2.7% reported in 19,193
infants whose mothers had an untreated depression and/or anxiety disorders during
pregnancy. No signicant difference was found in the risk of malformations in newborns exposed to BDZ as well as in Z-drugs in early pregnancy (Ban etal. 2014).
Overall, it could be concluded that data on the safety of zolpidem and zopiclone
seems quite reassuring as far as the risk of major birth defects in newborns exposed
in the rst trimester of pregnancy is concerned. However, more studies are needed
to conrm this reassuring data, as insomnia and sleep difculties are common complaints during pregnancy. Notwithstanding, despite the importance of sleep during
pregnancy, current understanding of the prevalence of prenatal insomnia and associated risk and protective factors is limited. Estimates of the prevalence of insomnia
symptoms vary from 20% to 60% depending on the sample, the assessment measure
used in the investigations as well as the population investigated.
12.5 Perinatal Complications
12.5.1 Benzodiazepines andZ-Drugs
Since a relevant number of pregnant women take a BDZ or a Z-drug during the
perinatal period, the question of their gestational and neonatal safety is not trivial.
BZDs and Z-drug exposure during pregnancy have been associated in some studies
with gestational and neonatal complications, such as preterm birth, low birth weight,
low Apgar score, spontaneous abortion, and a neonatal withdrawal or abstinence
syndrome (NWS). However, data published on these important topics have reported
contradictory results.
NWS is a condition affecting about 25% of newborns exposed late in pregnancy,
including signs such as somnolence, irritability, hypoglycaemia difculties with
sucking, tremors, tachypnoea, gastrointestinal upset, hypoglycaemia, and hyperreexia. The symptoms generally appear within a week after birth and can last from
few days up to 3/4 weeks. It has been suggested that gradually tapering the daily
dose of BZDs some weeks before delivery could be useful to minimize the neonatal
withdrawal symptoms, even though this strategy has not been shown to be helpful
in many cases of exposed newborns. In addition, a BZD discontinuation could
induce a withdrawal reaction in pregnant woman, especially among those who have
been taking higher doses of BZDs for several weeks during gestation. However,
most newborns presenting withdrawal symptoms improve and recover usually after
few days or weeks, without any long-lasting sequelae.
The use of BDZs, especially at high dosage, in most cases through intravenous
route before delivery has been associated with an “infant oppy syndrome” (IFS),
which is characterized by oppiness or general muscular hypotonia at birth or in
early life, affecting the limbs, trunk, and the cranial-facial musculature. However,
the IFS can be also induced by a variety of neuromuscular and central nervous
12 Benzodiazepines andZ-Drugs inPregnancy
297
system disorders, including genetic and/or metabolic decits, therefore its association with exposure to BZDs at high dose before delivery needs to be better investigated. A recent population-based cohort study including mother-child pairs from
2001 to 2018in Hong Kong compared gestationally exposed and nonexposed children to BDZs and Z-drugs to investigate the risk of preterm birth, small for gestational age, autism spectrum disorder (ASD), and attention-decit/hyperactivity
disorder (ADHD) through logistic/Cox proportional hazards regression. Siblingmatched analyses and negative control analyses were applied.
No statistically signicant differences were found for all outcomes investigated
when comparing children whose mothers took BDZs and/or Z-drugs during pregnancy to children whose mothers took such drugs before, but not during pregnancy.
In their discussion, the author indicates that many studies on this topic may be limited by small sample sizes, poor representativeness of data, recall bias, inadequate
adjustment of confounders such as indication (i.e., anxiety and/or sleep disorders)
and unmeasured variables such as illicit drug use (Chan etal. 2023). In the abovementioned retrospective cohort study by Jurich, 45 pregnant women who took zolpidem were more likely to have gestational hypertension and anaemia, as well as a
greater chance of a caesarean delivery compared to the untreated group. Rates of
preterm delivery and low birth weight were 26.7% and 15.6% respectively in the
zolpidem-exposed group versus 13.3% and 4.4% in the matched comparator group,
but no signicant differences were found. It was also found that zolpidem crosses
the human placenta and rapidly clears the fetal circulation; the degree of placental
passage in this sample was highly variable, with cord concentrations of zolpidem
ranging from 48% to 275% of maternal concentrations (Juric etal. 2009).
A large study was conducted in Norway to establish whether exposure to BDZs
or Z-hypnotics in pregnancy was associated with greater risk of negative immediate
pregnancy outcomes compared with non-exposed group. The main outcomes were
gestational age at delivery, risk of preterm delivery, birth weight, risk of being small
for head circumference, low Apgar score, and risk of neonatal respiratory distress.
It was found that children born to mothers who were exposed to these drugs in pregnancy had slightly lower birth weight and had slightly higher to moderately risk of
preterm birth compared with children without exposure. In their conclusions, the
authors rightly pointed out that while the magnitudes of the associations were not
necessarily clinically signicant, BDZs and Z-drugs are not rst-line treatment for
anxiety disorders and therefore should only be used in pregnancy after an accurate
evaluation of the benets and risks for the mother and child (Huitfeldt etal. 2020).
A large, case-control study found that, after adjusting for measured confounds,
early gestational exposure to BDZ was associated with a nearly doubled risk of
spontaneous abortion; the risks were higher with higher daily doses prescribed.
However, it must be observed according to Andrade that these ndings indicate
that BDZs are probably a marker since the results of the study are not evidence for
a cause-effect relationship, because analyses in studies such as this adjust for only
“measured” confounds; therefore, unmeasured, inadequately measured and
unknown confounds will continue to contaminate the interpretation of ndings.
Innovative research in this eld should be considered, such as the examination of
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risk associated with BDZ exposure in the year before pregnancy, examination of
risk in previously unexposed pregnancies as well of risk in discordant sibling pairs,
and examination of risk associated with paternal exposure. Such studies have the
potential to indirectly partially address unmeasured and unknown confounds,
including those related to genetics and the family environment (Andrade 2019b).
A recent study has been conducted in Norway exploring the association between
prenatal exposure to BDZs and Z-drugs and risk of ADHD in childhood (Sundbakk
etal. 2022). In total, 681 offspring (0.8%) in the full sample and 468 offspring
(2.4%) in the mental health sample were prenatally exposed to these medications.
The results of this clearly indicate that there is no increase in risk of childhood
ADHD associated with prenatal exposure to BDZs and/or Z-hypnotics. An original
large cohort study including 1.138732 mothers with 1.516846 live births was
recently published to assess the risk of ADHD and ASD in children exposed in utero
to anxiolytic and hypnotic drugs (Chin-Hung Chen etal. 2022). No statistically
signicant differences were found with unexposed sibling controls during the same
time frame for ADHD and ASD.Similar ndings were also noted in the stratication analysis of short-acting and long-acting BDZs. To our knowledge, no prior
studies have examined such an association using a sibling control method. The discordance in results between population and sibling comparisons suggests that
maternal psychological or physical conditions may be potential “unmeasured” confounders for poorer neurodevelopmental outcomes among offspring. These conditions might include other maternal anxiety and sleep disorders recognized to be
associated with neurodevelopmental problems among children. According to the
authors it is plausible to believe that rather than simply attributing neurodevelopmental disorders as a direct consequence of neonatal BDZs exposure during pregnancy, it can be more important to reduce neurodevelopmental disorders by
identifying mothers “at risk”.
As appropriately suggested by Andrade in a recent comment of this study, “the
associations between gestational exposure to BDZs and Z-drugs and ASD or ADHD
in offspring may be due to maternal and parental genetic factors, to family environmental variables, and to confounding by indication, rather than to such drugs exposure itself” (Andrade 2023). A recent systematic review including 19 selected
studies on this topic also conrms that it is currently not possible to conclude, with
a reasonable degree of certainty, whether prenatal exposure to BZDs and/or z-drugs
is associated with neurodevelopmental outcomes in offspring. This uncertainty
mainly originates from a remarkable scarcity and quality of overall research on this
important topic and therefore high-quality studies on the safety of BZD and Z-drug
use during different stages on fetal brain development are urgently needed (Wang
etal. 2022).
Overall, even though reassuring ndings have been documented in the studies
recently published on the risk of gestational and neonatal complications in women
exposed in utero to BDZs and Z-drugs, further studies focusing on short and longterm infant adverse outcomes are still needed, particularly those focusing on the
neurodevelopment disorders in children, as these disorders most likely have a multifactorial genesis.
12 Benzodiazepines andZ-Drugs inPregnancy
299
12.6 Conclusions
According to the recent cohort studies, overviews, and guidelines, BDZs and Z-drugs
exposure during early pregnancy seems not to be associated with an increased relative
risk of congenital major malformations. However, it should be observed that in a few
case-control studies but not in most cohort studies and meta-analysis a statistically signicant association between these drugs and major birth defects was found. To explain
the discrepancy in the results of such studies, it is worthwhile to consider that most of
the rst original investigations suffer from a number of methodological aws, such as
the lack of a careful report of BDZs and Z-drugs patterns of use in pregnancy (i.e., time
of exposure, dosages, reasons for drug prescription, etc.), possible inuences of recall
biases (linked to case-control design), and the lack of control of several confounding
factors (i.e., the presence of a severe psychiatric and /or organic disorder, alcohol abuse,
smoking, and concomitant medications).
The BZDs exposure during the second and/or third trimester of pregnancy was
found in some studies associated with an increased risk of neonatal and gestational
complications, particularly preterm birth, low birth weight, and low Apgar score.
However, even in this case, most of the above-mentioned adverse events were not
observed in well-designed clinical investigations which controlled for confounding
factors. On the other hand, there is a general agreement that BDZs could induce a
neonatal withdrawal or abstinence syndrome, but only when used in the last two trimesters of pregnancy at high dosages, and particularly in the case of very/extremely
preterm newborns. No increased risk concerning infant neurodevelopment and/or
cognitive impairment has so far been well established in the majority of studies and
reviews focusing on the safety of BDZs and/or Z-drugs exposure during pregnancy.
However, there is still a need to perform further prospective cohort studies, based on
adequate large samples, enrolling and following women from the rst prenatal visit
to the end of pregnancy and postpartum period, with a regular clinical monitoring of
their psychopathological conditions and drug treatment. Also, a long term standardized assessment of infants exposed to BZs during the perinatal period is crucial.
It is thus recommended to treat pregnant women with anti-anxiety and/or hypnotic drugs, only in the case of severe insomnia and/or acute anxiety, where other
effective therapeutic options, particularly psychological treatment, have failed.
Among the BDZs, it should be preferred as a rst-line option, those drugs with a
short-medium elimination half-life and with no active metabolites.
The dosage and length of an anxiolytic/hypnotic treatment should be individualized in each pregnant woman, with the aim to prescribe the “lowest but effective
dose”. Such clinical practice is clinically relevant to prevent or minimize neonatal
adverse effects, particularly the risk of withdrawal reactions. There is a need for
those working in the eld of perinatal mental health to improve their knowledge in
this matter, thinking that perinatal psychiatry as well as perinatal psychopharmacology are not merely new or emerging specialties but everyone’s business (Freeman
2014; Humphrey etal. 2016). Table12.2 provides recommendations on the use of
BDZs and Z-drugs in routine clinical practice during pregnancy, according to the
recent evidence-based information and clinical experience.
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Table 12.2
BDZs and Z-drugs during pregnancy should be prescribed to women affected by acute anxiety
symptoms and severe insomnia, where non-pharmacological treatments have failed or are not
effective enough to relieve such clinical conditions
BDZs are not indicated in monotherapy to treat women with general anxiety disorders, panic
disorders, obsessive-compulsive disorder, and major depression; in such psychopathological
conditions second-generation antidepressants, particularly SSRI, are usually recommended as
a rst-line pharmacological option in pregnancy
BDZs and Z-drugs should not be used for several months, but shortintermittent use is better to
avoid potential risk of dependence, tolerance, or misuse; the discontinuation must always be
carried out gradually, according to the dosage taken by the patient and the length of treatment
she is taking
When considering the risks and benets of anxiolytic and hypnotic drugs, clinicians should
also consider the risks of an untreated severe insomnia and/or acute anxiety in pregnancy,
which may lead to adverse biological effects as well as a reduced level of self-care, worsening
mood, and impaired functioning
BDZs and Z-drugs are no longer considered at risk of inducing major congenital malformation
as recent original studies and systematic reviews do not support such increased risk in
newborns exposed in the rst trimester of pregnancy as compared with newborns of unexposed
pregnant women
Exposure to BDZs during gestation was considered in some studies responsible for gestational
complications, particularly spontaneous abortion and preterm delivery. These ndings however
have not been replicated in recent original controlled studies. BDZ may be responsible in some
newborns of withdrawal reactions also called “abstinence-like syndrome” which in the most
cases improve in few days or a week, even though in preterm neonates could be longer (2/3
weeks), but without any long-lasting sequelae. This syndrome has been most frequently
reported when the mother has been treated with high doses of BDZs during the last trimester
of pregnancy
In pregnant women who are treated with high doses of BDZs an infant clinical monitoring by
a paediatrician during the rst month after birth is strongly recommended
The woman and her partner should be informed on the potential risks of the drug prescribed
and those concerning the non-treatment of severe anxiety and insomnia. Moreover, the
clinicians must be sure that all the information provided has been clearly understood
Informed signed consent should also be collected by the mother and her partner before
prescribing BDZs or Z-drugs, as in the case of other psychotropic treatment
The dosage and length of drug treatment must be accurately individualized in each woman to
better establish the lowest but effective therapeutic dosage
Among BDZs, drugs with short or medium elimination half-life and no active metabolites
(oxazepam-like agents) should be preferred as a rst-line choice for their better
pharmacokinetic and metabolic prole for the foetus and the pregnant
Women treated with BDZ and Z-drugs during pregnancy, as well as other psychotropic drugs,
should be advise to give birth in a general hospital where there is a neonatal intensive care
unit, in order to provide effective and timely treatment in case of neonatal severe adverse
reactions; this is particularly important in case of extremely preterm births (< 28weeks of
gestational age)
Expert recommendation based on scientic evidence and clinical experience
12 Benzodiazepines andZ-Drugs inPregnancy
301
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