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450
L. Orsolini et al.
Lemoine 2012). Subsequently, Jones and Smith clearly described this specic spectrum of dysmorphologies associated with AUD during pregnancy and rstly introduced the associated terminology ‘Fetal Alcohol Syndrome’ (FAS) (Jones et al.
1973). FAS is a clinically complex congenital disorder of the fetus determined by
the mother’s consumption of alcohol during pregnancy (Seo etal. 2021; Hur etal.
2022). Indeed, it has been demonstrated that alcohol consumption occurring also
from around 3–4months before conception and throughout the pregnancy can affect
fetal development. The prevalence of FAS in the general population is 14.6 per
10,000 people. In addition, it has been estimated that one out of 67 pregnant women
who consumed alcohol will have a child developing a FAS, resulting in approximately 119,000 babies born with FAS each year worldwide (Popova etal. 2017; Hur
et al. 2022). The FAS is characterized by craniofacial, limb, and cardiovascular
defects associated with prenatal-onset growth deciency and development delay
(Jones etal. 1973; Seo etal. 2021; Hur etal. 2022).
Indeed, another not-full FAS condition was also identied and described within
the terminology of ‘foetal alcohol spectrum disorders’ (FASD). FASD is represented by a pattern of dysmorphologies comprising all not-fully FAS clinical presentations. FASD is an umbrella term describing the range of developmental
deviations, such as craniofacial mal-development or neurodevelopmental abnormalities that can occur in an individual whose mother consumed alcohol during
pregnancy (Hoyme etal. 2016). FASD may include a low birth weight, preterm
birth, small for gestational age, spontaneous abortions, behavioural problems,
developmental delay, cognitive decits, related to dose-response pattern to alcohol
use during pregnancy (Blume 1985; Streissguth et al. 1989; Sood et al. 2001;
O’Callaghan etal. 2007; Sayal etal. 2007; Patra etal. 2011).
Overall, the extent of developmental abnormalities seemed to depend on the prenatal alcohol amount, pattern of consumption, and timing throughout pregnancy. No
level of alcohol consumption is safe during pregnancy. Binge drinking in the rst
6 weeks of pregnancy and chronic alcohol consumption throughout pregnancy,
which is often associated with poor maternal nutrition and reduced BMI, have been
reported to be associated with the highest incidence of FASD (Grzywacz et al.
2023). However, many etiopathogenetic determinants, including genetic, epigene-
tic, and social environmental factors, may also inuence the development and manifestations of FASD and associated disabilities (Murawski etal. 2015). Approximately
30–40% of children with signicant prenatal alcohol exposure meet the criteria for
FASD (Grzywacz etal. 2023). Most children affected with FASD may experience
difculties in daily life, e.g., decit in motor control, eyesight, hearing, attention,
concentration and impulse control (Riley etal. 2011). Furthermore, it has been documented the association between FASD and the development of autism spectrum
disorder (ASD), attention-decit-hyperactivity disorder (ADHD), and intellectual
disability in newborns exposed to antenatal maternal alcohol consumption (Popova
etal. 2016).
FASD is a broad diagnosis which includes four distinct diagnostic categories: (a)
classical FAS; (b) fetal partial alcohol syndrome (PFAS); (c) alcohol-related neurodevelopmental disorder (ARND); and (d) alcohol-related birth defects (ARBD)
21 Alcohol Use Disorders
451
(Hoyme etal. 2016). FAS refers to those babies who full all complete/classical
criteria and comprise facial dysmorphologies, growth inhibition and dysfunction of
the central nervous system (Hoyme etal. 2016). Children with FAS display central
nervous system abnormalities (i.e., microcephaly, tremors, hyperactivity, lack of
motor skills, attention decit, learning disabilities, intellectual or cognitive decits,
and seizures), a pre and/or postnatal growth disturbance and characteristic facial
abnormalities (i.e., hort eyelid slits, epicantal folds, at midface, hypoplastic philtrum, and a thin upper vermilion border) (Hoyme etal. 2016). Diagnosis is often
overlooked, misdiagnosed, or delayed, with an average delay of about 48.3months
after birth, which prevents affected children from receiving necessary services
promptly. To diagnose FAS, physicians must collect a detailed history related to
prenatal alcohol exposure. Signicant exposure is dened as at least one of the
following:
• 6+ drinks per week for 2+ weeks during pregnancy
• 3+ drinks per occasion on 2+ occasions during pregnancy
• Alcohol-related social or legal issues during pregnancy.
• Documented intoxication via blood, breath, or urine tests.
• Positive alcohol biomarkers (e.g., fatty acid ethyl esters, phosphatidylethanol) in
maternal or fetal samples.
• Increased prenatal risk from alcohol use identied by a validated screening tool.
If there was no history of prenatal alcohol use in the 3months before recognizing
pregnancy or at the time of a positive test, FAS can be excluded (Hoyme etal. 2016;
Hur etal. 2022). A summary of the FAS diagnostic process has been provided in
Table21.2. Updated diagnostic criteria for the diagnosis of fetal alcohol spectrum
disorders are reported in Table21.3.
21.4 Prenatal Alcohol Exposure andChildren’s Outcomes
Several studies documented an increased risk of unfavourable outcomes in children
of mothers with heavy prenatal alcohol consumption. These include a range of
behavioural problems, developmental challenges, as well as more severe outcomes
such as intellectual disability, cerebral palsy, preterm birth, low birth weight, stillbirth, sudden infant death syndrome (SIDS), and infant mortality (Mattson etal.
2013; Flak etal. 2014; Hutchinson etal. 2014). These outcomes are attributed to
both the biological effects of prenatal alcohol exposure and social/environmental
factors including increased risk of parental mental health problems, other substance
use, economic disadvantage, family instability, poor parenting skills and social isolation (O’Leary etal. 2020).
Prenatal alcohol exposure (PAE) has been associated with several neurodevelopmental decits, including attention difculties, learning delays, poor memory and
impaired social skills. Children prenatally exposed to alcohol may face behavioural
problems, poor academic performance, and interactions with the justice system.
452
L. Orsolini et al.
Table 21.2
1. Evidence of prenatal or postnatal growth
impairment, in at least 1 of the following (FAS
only):
2. Simultaneous presentation of the following
facial anomalies at any age (FAS all 3, partial
FAS any 2):
3. Evidence of impairment in 3 or more of the
following CNS domains (FAS, partial FAS, and
ARND):
4. Conrmed maternal alcohol exposure (partial FAS)
SD standard deviation, CNS central nervous system, IQ intelligence quotient
a
FAS can be diagnosed without this if (1) to (3) are all present
Criteria for FAS and partial FAS
Birth weight or birth length at or below
the tenth percentile for gestational age
Height or weight at or below the tenth
percentile for age
Disproportionately low weight-to-height
ratio at or below the tenth percentile
Short palpebral ssure length (2 or more
SDs below the mean)
Smooth or attened philtrum (rank 4 or 5
on the lip-philtrum guide)
Thin upper lip (rank 4 or 5 on the
lip-philtrum guide)
Hard and soft neurologic signs
Brain structure
Cognition (IQ)
Communication
Academic achievement vi. Memory
Executive functioning and abstract
reasoning
Attention decit/hyperactivity
Adaptive behaviour
Social skills
Social communication
a
ADHD is a neurodevelopmental disorder and is the most frequently diagnosed cognitive and behavioural disorder among school-age children, with an estimated
worldwide prevalence of 7.2% for children and adolescents and 2.5% for adults
(Chaulagain etal. 2023). The aetiology of the disorder remains unclear, despite
several genetic and environmental factors having been proposed to increase susceptibility to the disorder, one of which is PAE (Banerjee etal. 2007; Wetherill etal.
2018; Gibson and Porter 2022). This could be related to an altered brain develop-
ment, which appears to be negatively affected by prenatal exposure to alcohol, with
PEA being associated with reduced brain volume and subsequent attention difculties and impulsivity (Lebel etal. 2011; Paolozza et al. 2014). Studies in animal
models also indicated that even low levels of prenatal alcohol exposure can negatively affect neurodevelopment. For instance, reduced brain volume and response
inhibition decits have been documented in individuals with PAE, highlighting its
long-lasting impact on cognitive and behavioural functioning (Sood etal. 2001).
However, data from the current published literature appeared contradictory, with
some studies indicating that prenatal alcohol consumption—whether light, moderate, or heavy—is not associated with an increased risk of ADHD in offspring
(Mitchell and Sevigny-Resetco 2020).
The effect of PAE also seemed to depend on a set of genetic factors. A recent
study by Miyake etal. (2024) aimed at investigating the role of polymorphisms of
21 Alcohol Use Disorders
453
Table 21.3
alcohol spectrum disorders
FAS With or without documented prenatal alcohol exposure
PFAS With or without documented prenatal alcohol exposure
ARND This diagnosis cannot be made before the age of three.
ARBD Requires all the following features:
FAS fetal alcohol syndrome, PFAS partial fetal alcohol syndrome, ARND alcohol-related neurode-
velopmental disorder, ARBD alcohol-related birth defect
Updated Institute of Medicine (IOM) diagnostic criteria for the diagnosis of fetal
Requires all the following features:
A characteristic pattern of facial anomalies, including at least 2 among the
following: (1) short palpebral ssures; (2) thin vermilion border of the upper lip;
(3) smooth philtrum
Prenatal and/or postnatal growth deciency
Decient brain growth, abnormal morphogenesis or abnormal neurophysiology,
including at least 1 of the following head circumference ≤10th percentile; (1)
structural brain anomalies; (2) recurrent nonfebrile seizures (other causes of
seizures having been ruled out)
Neurobehavioural impairment
Requires all the following features:
A characteristic pattern of facial anomalies, including at least 2 among the
following: (1) short palpebral ssures; (2) thin vermilion border of the upper lip;
(3) smooth philtrum
Neurobehavioural impairment
Requires all the following features:
Documented prenatal alcohol exposure
Neurobehavioural impairment
Documented prenatal alcohol exposure
One or more specic major malformations due to prenatal alcohol exposure: (1)
cardiac (atrial septal defects, aberrant great vessels, ventricular septal defects,
conotruncal heart defects); (2) skeletal (radioulnar synostosis, vertebral
segmentation defects, large joint contractures, scoliosis); (3) renal (aplastic/
hypoplastic/dysplastic kidneys, ‘horseshoe’ kidneys/ureteral duplications); (4) eyes
(strabismus, ptosis, retinal vascular anomalies, optic nerve hypoplasia); (5) ears
(conductive hearing loss, neurosensory hearing loss)
the ADH1B and ALDH2 genes, both demonstrated to be involved in alcohol metabolism, in maternal alcohol consumption during pregnancy and their association with
the risk of developmental delays in offspring in a Japanese population. Analysis of
maternal polymorphisms of the ALDH2 gene showed that alcohol consumption by
mothers with wild-type genotype specically increased the risk of communication
delays. In contrast, mothers with the heterozygous genotype were associated with
an increased risk of developmental delays (Miyake etal. 2024). While the inuence
of the polymorphism of the ADH1B gene on developmental outcomes could not be
clearly determined (Miyake etal. 2024).
PAE has also been reported to be associated with the increased probability of
alcohol and substance use in adolescents, but its specic impact is difcult to determine because of concomitant risk factors, including parental substance use, home
environment, access to substances and genetics (Jacobson etal. 1998). The impact
of PAE seems to depend on drinking patterns, with binge drinking causing the most
454
harm (Duko etal. 2020, 2022). Streissguth’s Seattle 500 study showed that PAE is
more predictive of adolescent alcohol use at age 14 than family history of alcohol
problems (Baer etal. 1998, 2003). The Mater University study of Pregnancy showed
that maternal consumption of more than 3 drinks is more predictive of alcohol use
at age 14 (Alati etal. 2008). In contrast, according to another study, strong PAE in
the rst trimester predicted higher alcohol consumption in offspring at 16 and
22years of age, regardless of childhood behavioural problems or family history of
alcohol use (Goldschmidt etal. 2019). In a study conducted by Dodge etal. (2023),
PAE has been reported to signicantly impact on the amount of alcohol consumed
per occasion and on tolerance, rather than on the frequency of consumption, much
more likely due to an increased sensitivity to the rewarding effects of alcohol.
L. Orsolini et al.
21.5 Alcohol Intake During Breastfeeding andChildren’s
Outcomes
There is limited research available on the alcohol use during lactation. It is known
that alcohol passes rapidly to breast milk, where it is found in a similar concentration to maternal blood (CDC 2024). It has been documented that alcohol intake
during breastfeeding may have a negative impact on infant brain development,
being also associated with the development of detrimental cognitive and academic
outcomes (Haastrup etal. 2020). Alcohol use during lactation has also been associated with an increased prevalence of ADHD and altered infant sleep patterns
(Haastrup etal. 2020; Gibson and Porter 2020). However, the literature reports conicting data with some studies, such as that carried out by Gibson and colleagues
showing no correlation between maternal alcohol consumption during breastfeeding and the risk of ADHD or ASD (Gibson and Porter 2022). Alcohol intake while
breastfeeding may still be harmful to children or disrupt the lactation process when
consumed during breastfeeding. For this reason, the safest choice for breastfeeding
women seems to be abstaining from alcohol consumption (Gibson and Porter 2018,
2020, 2022).
21.6 Screening Tools forAUD During Pregnancy
An increased predisposition to the development of AUD has been observed during
the reproductive age, especially in the presence of comorbid psychiatric or neurodevelopmental disorders (e.g., ADHD) (Luderer etal. 2021). Most women who use
alcohol more commonly reduce their consumption during pregnancy. Generally,
women avoid initiating the use of potentially harmful substances once they become
aware of their pregnancy. Those capable of quitting independently typically manage
to do so (Prince etal. 2023). Approximately half of pregnant women report drinking
shortly before pregnancy, with more than 10% who display a binge drinking pattern
that is also being associated with a higher risk of subsequent alcohol consumption
during pregnancy (Naimi etal. 2003; Kitsantas etal. 2014).
21 Alcohol Use Disorders
455
Hence, a careful and prompt identication of AUD and/or risky alcohol intake
could help clinicians to provide an appropriate and timely support before/during/
after pregnancy which has been suggested to be crucial for maternal and neonatal
health (McGovern etal. 2021; Prince etal. 2023). A thorough medical history and
physical examination often reveal an alcohol use. However, many women do not
disclose sensitive information about their alcohol intake, so doctors must rely on
other methods to identify those women at-risk to be diagnosed with AUD.Ideally,
all pregnant women should be screened and those who test positive should be
treated, with access to effective interventions if indicated, as part of comprehensive
antenatal care in collaboration with pregnant women (ACOG 2018; Prince
etal. 2023).
Regarding the clinical assessment, clinicians currently have several validated
screening tools for AUD such as the CAGE (Cut down, Annoyed, Guilty, Eyeopener) (Ewing 1984), the Alcohol Use Disorders Identication Test (AUDIT-C)
(Saunders etal. 1993), the Michigan Alcoholism Screening Test (MAST) (Selzer
1971), the Tolerance, Worried, Eye-opener, Amnesia, K/Cut down attempts
(TWEAK) (Russel etal. 1994) and the Tolerance, Annoyance, Cut down attempts,
Eye opener (T-ACE-R3) (Chang etal. 1998). However, several of these screening
tools have not been specically developed and/or validated for the pregnant population (such as the CAGE and MAST tools), either they have been designed to accurately identify alcohol use patterns in male samples, by particularly focusing on
alcohol dependence. Hence, they may be less effective in identifying problem
drinking amongst women, especially among pregnant and/or nursing women.
Therefore, positive cut-off scores for these AUD screening tools need to be set differently for women than for men. In fact, women usually experience higher blood
alcohol levels at identical exposures (doses) and women are more susceptible to
irreversible and severe alcohol-dependent organ damages, compared to the male
counterpart (Urbano-Marquez etal. 1995; Graham etal. 1998; Jones etal. 2013). So
far, only T-ACE, TWEAK, AUDIT-C, 4P’s Plus and the 1-Question Screen have
been validated for AUD screening in pregnant women. In particular, T-ACE,
AUDIT-C, and TWEAK questionnaires are considered the most promising screening tools for detecting at-risk alcohol drinking in pregnant women (WHO 2014;
Montag 2016; Poole etal. 2019; Chang 2020; Dozet etal. 2023). However, a positivity to the screening tools, it appears to not be enough to take a diagnosis, being
needed to be accompanied by a structured and complete clinical interview about the
frequency of alcohol intake and current alcohol pattern. Finally, laboratory-based
screening tools could be useful to measure prenatal alcohol exposure through ethanol biomarkers, such as fatty acid ethyl esters, found in blood, maternal and neonatal hair, placenta, cord blood, and meconium (Prince etal. 2023).
456
L. Orsolini et al.
21.7 Pharmacological Management ofAlcohol Use Disorders
During thePerinatal Period
The optimal management strategy for pregnant women with AUD includes pharmacological treatment, consultation with a multidisciplinary team comprising several
specialists, and psychosocial interventions. A psychoeducational approach (also
preventive) addressed to at-risk pregnant women, those not still pregnant women
who intend to start a pregnancy and those displaying risky factors associated with a
higher probability to develop an AUD and/or a risky alcohol intake should be the
rst therapy target strategy. The rst recommendation should include educating
about the consequences of alcohol intake during pregnancy for both the mother and
the fetus in the short- as well as in the long-term (US Preventive Services Task Force
2018). The second recommendation should provide advice to refer to the speciality
treatment service, incentivize access and ask for professional help for the management of alcohol intake and act by using a harm reduction strategy (US Preventive
Services Task Force 2018). Motivational interviewing and brief interventions are
more effective than judgmental or punitive approaches in encouraging positive
behavioural change (Prince etal. 2023). Patient education, counselling, and monitoring do not end with childbirth, as women with AUD are at the highest risk of
developing a postpartum relapse and must be educated about the dangers of resuming substance use after childbirth. They need to be closely monitored, particularly
during the rst postpartum year. Psychosocial interventions appear to reduce the
frequency of alcohol intake by parents. Integrated interventions that combine parenting skills with an alcohol use component seem to be the most promising, although
it appears that mothers may benet less from these interventions than fathers
(McGovern etal. 2021). Peer support groups seem to be very helpful (Forray etal.
2015; Morton Ninomiya etal. 2023).
Overall, there is limited evidence regarding the potential risks associated to pharmacological treatment prescribed by clinicians to those at-risk and/or those pregnant women affected by AUD (Briggs and Freeman 2015). The highest risk could
be much more likely during an explosion to pharmacotherapy during the rst trimester of pregnancy (Mitchell etal. 2011). The American Psychiatric Association
(Reus et al. 2018) recommends that for pregnant or nursing women with AUD,
pharmacological treatments should not be prescribed, except for managing an acute
alcohol withdrawal through BZDs or for managing a dual disorder (i.e., a concomitant psychiatric disorder) (ACOG 2018).
Regarding the pharmacotherapy for AUD, there are a number of approved medications used for the treatment of AUD including naltrexone, disulram, acamprosate, nalmefene, and baclofen, as well as repurposed topiramate and gabapentin
(Burnette etal. 2022). However, the use of these medications in pregnancy is typically not recommended due to the unknown fetal risks and the lack of evidence
regarding the long-term safety and efcacy. Indeed, there is also a lack of agreement
between health organization guidelines for the pharmacological management of
AUD in pregnancy. Some guidelines suggest that relapse prevention medications
should not be initiated in pregnant women, due to the low level of evidence
21 Alcohol Use Disorders
457
(Lingford-Hughes etal. 2012; Rolland etal. 2016; Reus etal. 2018; Thibaut etal.
2019). Some guidelines also recommend to consider the management on a case-by-
case basis (Lingford-Hughes etal. 2012; Rolland et al. 2016; Reus etal. 2018),
particularly in those women on alcohol pharmacotherapy prior to conceiving.
Overall, data coming from animal studies do not recommend the use of disulram
due to the lack of supporting studies, while a moderate risk is associated with the
use of naltrexone and a high risk with acamprosate, a possible risk for use of gabapentin and topiramate (Briggs and Freeman 2015). Regarding breastfeeding, even
though limited data is available, there may be potential for toxicity with disulram,
naltrexone and topiramate (Briggs and Freeman 2015), whereas acamprosate and
gabapentin are noted to be ‘probably compatible’ with breastfeeding (Briggs and
Freeman 2015).
21.7.1 Naltrexone Use
Naltrexone is a mu opioid receptor antagonist that has been shown to decrease the
risk of heavy drinking to 83% of the risk in placebo groups and decrease drinking
days by about 4% (Rösner etal. 2010). Naltrexone is available in both oral and longacting injectable formulations. However, there are no published studies on the safety
or efcacy of either formulation of naltrexone for use in AUD in pregnant women.
Naltrexone is classied as a category C medication by the Food and Drug
Administration (FDA), meaning that animal studies have shown adverse effects on
the fetus, but there are no adequate studies on reproductive effects and safety in
human pregnancy (Zagon etal. 1998). In fact, a small number of clinical studies has
examined the safety of naltrexone in pregnancy, by indeed investigating the treatment of pregnant women with opioid use disorders and not AUD (Hulse and O’Neil
2002; Hulse etal. 2001, 2004; Kelty and Hulse 2017a, b, c; Towers etal. 2020). A
retrospective cohort study of birth outcomes in neonates exposed to naltrexone in
utero reported that naltrexone-exposed neonates were generally not signicantly
different to buprenorphine-exposed neonates (n=124), but signicantly lower rates
of neonatal abstinence syndrome (7.5 vs. 41.8%) and shorter hospital length of stay
(5.5 vs. 8.0days) in naltrexone-exposed neonates. Compared with the control group
of neonates (n=569), naltrexone-exposed neonates were not signicantly different
in terms of overall rates of congenital anomalies, stillbirths and neonatal mortality.
However, naltrexone-exposed neonates were signicantly smaller (3137.1 vs.
3378.0g), spent more time in hospital following birth (5.5 vs. 4.3days) and had
higher rates of NAS (7.5 vs. 0.2%) (Kelty and Hulse 2017a, b, c). Despite concerns
about higher rates of some pregnancy complications, the general consensus is that
naltrexone is the safest option than alcohol use during pregnancy (Quintrell etal.
2025). Based on the currently available data, and the known teratogenic effects of
alcohol exposure, naltrexone would likely be the rst to be considered in the treatment of AUD in pregnancy.
458
L. Orsolini et al.
21.7.2 Disulfiram Use
Disulram (an aldehyde dehydrogenase inhibitor that results in a severe reaction
when alcohol is consumed concurrently with it, resulting in a strong deterrent effect)
is also a category C medication. There are no clinical studies on disulram exposure
in pregnancy. This is probably due to research conducted between the 1970s and
1980s (Nora etal. 1977; Gardner and Clarkson 1981; Dehaene et al. 1984) that
demonstrated an association between disulram use in pregnancy and an elevated
risk of adverse neonatal health outcomes, including congenital anomalies, miscarriages and stillbirths, probably due to the mechanism of action (Briggs etal. 2017).
There is some evidence, albeit inconsistent, that exposure to disulram in the rst
trimester may increase the risk of fetal malformations (Nora etal. 1977; Helmbrecht
and Hoskins 1993; Reitnauer etal. 1997). Furthermore, the intensity of the disulram-alcohol reaction, which can involve severe acute autonomic instability, including hypertension, can also be considered a risk to the pregnant woman and her fetus,
although there have been no studies specically assessing the magnitude of this
specic risk. While the only three preclinical studies on disulram exposure during
pregnancy present conicting ndings (Harding and Edwards 1993; Johnson etal.
2007; Teng etal. 2023). Therefore, although there was an absence of safety data on
the use of disulram in pregnancy, it is thought to be harmful and should not be used
(Quintrell etal. 2025). In particular, limited data documented that disulram acts as
a copper chelating agent, lowering blood and tissue copper levels which can harm
the pregnancy and the exposed neonate causing early embryonic death, congenital
anomalies and impaired cognitive and behavioural function. Moreover, combination of disulram and alcohol causes severe autonomic instability including dizziness, tachycardia, and so forth which are risk factors for pregnant women and their
developing fetus (DeVido etal. 2015).
21.7.3 Acamprosate Use
Acamprosate, which is believed to exert its action through modulation of glutamate
neurotransmission thereby reducing post-acute withdrawal symptoms and consequently helping to maintain sobriety, is also a category C medication (Rösner etal.
2010). Animal data suggest possible teratogenic effects of acamprosate, but there
are no human trial data to support this evidence. Overall, animal studies indicate
that prenatal exposure to acamprosate was not associated with adverse maternal or
neonatal health outcomes, nor with neurodevelopmental or behavioural impairments (Kelty etal. 2019). The same study did not report any stillbirths or neonatal
deaths, and there was no difference in rates of low birth weight, preterm birth or
congenital abnormalities between acamprosate-treated pregnant women versus
those not exposed (Kelty etal. 2019). However, the effects of acamprosate on shortterm memory remain unclear (Quintrell etal. 2025). A study by Quintrell etal.
(2023) suggested a potential neuroprotective action exerted by acamprosate against
damage caused by alcohol exposure in utero. Therefore, as very minimal research
21 Alcohol Use Disorders
has been conducted on the safety of acamprosate in pregnancy, preliminary evidence has suggested little cause for concern. In the few studies carried out, there
were no adverse effects associated with prenatal exposure to acamprosate (Quintrell
et al. 2025). However, further research is needed to draw denitive conclusions
about considering acamprosate as a rst-line pharmacotherapeutical approach for
the treatment of AUD in pregnancy.
459
21.7.4 Nalmefene Use
Nalmefene is produced in tablet form and approved by the European Medical
Agency (EMA) in 2013 for the treatment of AUD (EMA 2022). The oral formulation has not still approved by the FDA in the USA and is therefore unavailable. No
human or preclinical/animal studies investigating the safety of nalmefene in
pregnancy.
21.7.5 Baclofen Use
Baclofen could be typically used in the treatment of AUD as off-label medication,
except for the more recent approval in France (Rolland etal. 2020). Few animal
studies investigating the use of baclofen in pregnancy reported a risk of neural tube
defects (Briner 1996, 2001). Clinical studies on the safety of baclofen in pregnancy
are limited and do not allow to draw denitive conclusions.
21.7.6 Other Medications
Regarding other commonly prescribed medications for the treatment of AUD, topiramate was extensively investigated even though studies so far available did not
investigate its safety and use in AUD in pregnancy (Quintrell etal. 2025). Among
children exposed to prenatal topiramate has been documented the occurrence of an
increased risk for congenital anomalies (such as oral clefts, hypospadias), perinatal
complications (i.e., ischemic placental disease, preeclampsia, placental abruption,
small for gestational age, or preterm birth), increased risk of poor neurodevelopmental outcomes and intellectual disabilities including ASD, ADHD, learning disabilities (Quintrell et al. 2025). Furthermore, topiramate can induce weight loss
during pregnancy which may mediate the medication’s impact on fetal growth.
Although gabapentin was not found to be associated with an increased risk of major
congenital anomalies, several studies documented an increased risk of preterm
birth, small size for gestational age and neonatal intensive care unit (NICU) access
(Quintrell etal. 2025). Therefore, several concerns regarding the use of topiramate
and gabapentin in pregnancy have been identied and overall it is not recommended
to prescribe them to pregnant women.