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

org
Guidelines

Use of Psychoactive Substances during the Perinatal Period:

Guidelines for Interventions during the Perinatal Period from
the French National College of Midwives
Corinne Chanal1,2 , RM, Evelyne Mazurier1 , MD, Bérénice Doray3,4 , MD, PhD

Abstract: Based on their clinical practice and an extensive review of the literature, the authors propose a framework of procedures to be followed
to provide services to all women of childbearing age who use psychoactive substances (alcohol, cannabis, cocaine, amphetamines, and opioids),
especially during pregnancy or during the postpartum and breastfeeding periods, in view of their individual situations and environmental contexts.
J Midwifery Womens Health 2022;67(Suppl. 1):S17–S37  c 2022 The Authors. Journal of Midwifery & Women’s Health published by Wiley Period-
icals LLC on behalf of American College of Nurse Midwives (ACNM).

Keywords: women, pregnancy, breastfeeding, addiction, care

INTRODUCTION
The use of psychoactive substances (PS) during pregnancy
can have multiple physical, cognitive, and psychosocial
consequences for both mother and child. These recom-
mendations concern the following psychoactive substances:
alcohol, cannabis, cocaine, amphetamines, and opioids
(heroin, codeine, tramadol, morphine, opium, methadone,
and buprenorphine). Recommendations for tobacco use
and pregnancy have been issued by the French National
College of Obstetrics and Gynecology (Collège National des
Gynécologues-Obstétriciens Français, CNGOF) together with
the French Society for Tobacco Science (Société Française
de Tabacologie) and Public Health France (Santé Publique
France). These guidelines are intended to provide evidence-
based recommendations to perinatal professionals faced
with substance use in women of childbearing age and,
in particular, pregnant, postpartum, and breastfeeding
women.
METHODS
As this research was not intended to be exhaustive, we con-
ducted a narrative review of the literature focusing on the ar-
ticles we deemed most relevant. We identified scientific arti-
cles using key words or by manually searching the MEDLINE
database. Reports or recommendations drawn from existing
practices were searched manually on mainstream search en-
gines. We limited ourselves to documents published in En-
glish or French. Articles were selected based on reading titles
and abstracts. We concentrated on documents related to prac-
tices, determinants, effects, and preventive strategies related to
PS (excluding tobacco).
EPIDEMIOLOGY
All data are estimates based on self-report surveys and have
an inherent risk of underestimation.
Alcohol

1
Hôpital Arnaud de Villeneuve, CHU Montpellier, 371 avenue
du Doyen Gaston Giraud cedex 5, Montpellier, 34295, France
2
Réseau de Périnatalité Occitanie Espace Henri BERTIN
SANS, Bat A, 59 avenue de Fès–34080, Montpellier, France
3
Service de génétique, CHU de La Réunion, allée des Topazes,
cedex, 97405, SAINT-DENIS
4
Centre Ressource Troubles du Spectre de l’Alcoolisation
Fœtale (TSAF) - Fondation Père Favron - 43 rue du Four à
Chaux, Saint-Pierre, 97410, Réunion
Précis: Women of childbearing age and their partners must
be asked, especially during pregnancy, about psychoactive
substance use and should receive appropriate support from
perinatal professionals.
Correspondence
Corinne Chanal, Hôpital Arnaud de Villeneuve, CHU
Montpellier, 371 avenue du Doyen Gaston Giraud, 34295
MONTPELLIER cedex 5.
Email: c-chanal@chu-montpellier.fr
General population
According to the 2017 Baromètre Santé survey, 86.5% of 18 to
75-year-olds reported they had consumed alcohol in the past
12 months, 40.1% at least once a week, and 10.0% daily (15.2%
of men and 5.1% of women) (see Table 1).1 In 2017, 33% of men
and 14% of women aged 18–75 years exceeded the lowest risk
thresholds for consumption set by health experts and the pub-
lic authorities in 2019 (“do not consume more than 10 standard
drinks per week and no more than 2 standard drinks per day;
observe drink-free days during the week.”2
Among 17-year-olds, 85.7% reported they had already
drunk alcohol, 8.4% regularly (at least 10 times in one month),
and 44.0% had experienced a significant episode of binge
drinking in the past month. Binge drinking is drinking 5 drinks
or more on a single occasion (ie, 50 g of alcohol, with a stan-
dard French glass of 10 g of alcohol, compared with 14 g in the
United States).3

1526-9523/09/$36.00 doi:10.1111/jmwh.13419 S17

c 2022 The Authors. Journal of Midwifery & Women’s Health published by Wiley Periodicals LLC on behalf of American College of Nurse Midwives (ACNM).
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited and is not used for commercial purposes.
 15422011, 2022, S1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jmwh.13419 by Cochrane Colombia, Wiley Online Library on [07/10/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
✦ Pregnancies of women using psychoactive substances (alcohol, cannabis, cocaine, amphetamines, or opioids) are at higher
risk for both her health and that of her infant.
✦ Pregnant women require specific care before, during, and after the pregnancy.
✦ A person-first approach and responses to each patient’s needs improves pregnancy outcomes.
✦ Fluid, confident communication between pregnant women and health care providers, and among health care providers
themselves, are key points that should be improved

Table 1. Use of psychoactive substances in the general population tive actions implemented since 2010; it may also be due to dif-
according to Baromètre Santé 2017 (1) ferences in methods between the studies, but also to greater
Substance Type of use Men% Women% underreporting. Current estimates based not on self-report
Cannabis Use in past year 15.1 7.1
but rather on biomonitoring data suggest higher consumption
(between 15% in the Scottish study of meconium in 235 babies
Regular use 5.4 1.8
by Abernethy et al. and 62.7% in the Spanish study of hair from
Daily use 3.4 1.1 153 women by Gomez-Roig et al.).7–11
Cocaine Use in past year 2.3 0.9 These figures may also be underestimated as they often do
Crack Use in past year 0.3 0.1 not take into account consumption before discovery of preg-
nancy. A 2017 Australian study showed that 60% of women
Amphetamines Use in past year 0.5 0.1
had drunk between conception and pregnancy diagnosis ei-
MDMA/Ecstasy Use in past year 1.5 0.6 ther significantly and/or in a binge drinking pattern. This pro-
Heroin Use in past year 0.3 0.1 portion declined to 18% after the diagnosis.12

Women of childbearing age
In the 2017 Baromètre Santé survey, which included 4169
women aged 18 to 39 years, 77.6% said they had consumed
alcohol in the past 12 months and 21.5% at least once a week;
13.2% reported binge drinking at least once a month in the
past 12 months.4
Regular consumption mainly involves older women,
while younger ones report more recent episodes of intoxica-
tion (in proportion and frequency) and repeated binge drink-
ing. Half of 17-year-olds report this binging practice, which
continues to increase, especially among girls.3
Breastfeeding women
In a 2014 study based on 41 selected publications, Haarstrup
et al. found that about half the women in Western countries
consume alcohol while breastfeeding.13 In a 2017 study, 674
French breastfeeding mothers responded to a questionnaire
on frequency of alcohol consumption and binge drinking dur-
ing the previous month. It found that 0.4% had consumed
alcohol daily during pregnancy and breastfeeding. During
breastfeeding, 6.8% reported one or more episodes of binge
drinking.6
Other Substances

Pregnant women General population

In the 2010 French Perinatal Survey, 23% of pregnant women
reported having drunk alcohol at least once during their
pregnancy, and 19.7% of them after they were diagnosed as
pregnant.5 In 2012, of the 3063 pregnant or breastfeeding
women surveyed by telephone as part of a national survey,
51.4% reported they had drunk alcohol before pregnancy; 8%
reported at least one episode of binge drinking early in preg-
nancy and 1.2% late in pregnancy.6 In the 2017 Baromètre
Santé survey, 11.7% of 1614 mothers of children aged 4 years or
younger reported drinking during their last pregnancy: 10.7%
on special occasions only, less than 1% between once a week
and once a month, and less than 1% once a week or more. The
oldest women (35 years or older) and the most educated (post-
secondary degrees) were most likely to report having con-
sumed alcohol.4
This reported decrease from 23% to 11.7% could reflect a
favorable change in behavior possibly related to the preven-
Of all the illegal psychotropic substances, cannabis is by far
the most commonly used in France. According to the 2017
ESCAPAD survey, 39.1% of 17-year-olds in continental France
said they had smoked cannabis in their lifetime. Regular use
levels vary between girls and boys by a factor of more than 2
(4.5% vs. 9.7%). Among women, 19% of those aged 18 to 25
years, 11% of those 26 to 34 years, and 5% of those 35 to 44
years reported they had smoked cannabis at least once during
the past year.14 Adolescents who had dropped out of the school
system reported regular use 3 times higher than that of those
still in school (21.1% vs. 6.0%). The proportion of young peo-
ple at risk for problematic use or dependence (assessed with
a simple questionnaire, the Cannabis Abuse Screening Test or
CAST) was 7.4%.3
Experimentation is rarer for other illegal substances: 5.6%
for cocaine, 5.0% for MDMA/Ecstasy, 5.3% for hallucinogenic
mushrooms, and less than 3% (stable between 2014 and 2017)

S18 Volume 67, No. S1, November/December 2022


for LSD, amphetamines, heroin, and crack.14 In 2017, 6.8% of
adolescents in continental France reported having used an il-
legal substance other than cannabis at least once in their life.
According to ESCAPAD survey data, experimentation levels
remain between 3 and 4% for the substances most commonly
used (3.4% for MDMA/Ecstasy) and less than 1% for those
used least often (eg, 0.7% for heroin).3
According to the 2017 Baromètre Santé survey, 5.2% of
18 to 25-year-olds experimented with cocaine in 2017, versus
7.1% in 2014. As in 2014, experimentation was more common
among adults aged 26 to 34 years (10.2%). The past-year co-
caine use rate continued to increase significantly, from 0.2% in
1995 to 1.1% in 2014 and 1.6% in 2017.14 This increase mainly
involved men (whose past-year use rose from 1.5% to 2.3% be-
tween 2014 and 2017) and adults older than 25 years.
In France, the number of female heroin users was esti-
mated at 50,000. In 2015, 35,000 women with a mean age of
38 years received reimbursement for opiate replacement ther-
apy (ORT: methadone or buprenorphine).15
Pregnant women
Studies consistently show that at least 3% use cannabis in the
year of pregnancy.16 Women with depression are more than 3
times as likely to use cannabis during this period.14,16
Data about cocaine, heroin, and opiate replacement drug
use in pregnant women are extremely sparse. A retrospec-
tive study of 22,002 women who gave birth between Jan-
uary 1, 2011, and December 31, 2013, found that weak opi-
oids (codeine, opium, tramadol) had been prescribed and dis-
pensed to 1.4% of women and strong opioids (morphine, oxy-
codone, fentanyl) to 0.03% during their third trimester.17
CONTEXT AND DETERMINANTS OF PSYCHOACTIVE
SUBSTANCE USE
The risk of PS misuse in women is significantly lower during
pregnancy. Having a healthy child is therefore motivation for
them to reduce or stop using them. If the child is their sole
motivation, however, their risk of postpartum relapse is sig-
nificant.
However, the risk cofactors associated with PS use during
pregnancy include:
• maternal factors18–22 : young age, unwanted pregnancy, late
discovery of pregnancy, insufficient prenatal care, living
alone, urban living, low socioeconomic status, history of
imprisonment, history of sexual, physical, or emotional vi-
olence, especially child abuse (50%–80% of women with
substance use disorders have experienced trauma), post-
traumatic stress disorder (30 to 59% of people with sub-
stance use disorders have posttraumatic stress disorder),
mental health problems, low self-esteem, mood or person-
ality disorders, family conflicts, use of substances outside
of pregnancy, and use of another PS.
• genetic factors: the ability to eliminate alcohol via the hep-
atic enzyme system varies across populations and individ-
uals
• partner-related factors, especially the more or less sys-
tematic use of alcohol, tobacco, or illegal drugs, and
violence.23–28
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• use-related factors: in women, the practice of binge drink-
ing seems to be associated with a greater risk of contin-
uing this consumption pattern during pregnancy (55% vs
29%).29 Use of one substance increases the risk of using one
or more other substances.20,30–31
• pregnancy-related factors: pregnancy is a difficult time that
increases a woman’s vulnerability, potentially reveals pre-
vious trauma, and can promote drug use. Pregnant women
who use cannabis have been shown to have more criteria
for cannabis use disorders than non-pregnant women of
childbearing age using it (18.1% vs. 11.4%). Substance use
can also serve specific functions during pregnancy, such as
reducing anxiety or stress (alcohol, cannabis) or relieving
nausea (cannabis).
EFFECTS OF PSYCHOACTIVE SUBSTANCES
Effects on the Individual
Alcohol
For a given amount ingested, the plasma ethanol concentra-
tion is higher in women than in men. Since they metabo-
lize alcohol more slowly, they are more vulnerable to its toxic
effects.32,33 These may be acute (risk of faster onset of apa-
thy and drowsiness, increasing vulnerability to the environ-
ment, loss of self-control, and increased risks of unprotected
sex and sexual assault), or chronic (weight gain, higher and
earlier risk of skin aging, neurocognitive disorders in binge
drinkers, menstrual cycle disorders, cancer, especially of the
breast), cirrhosis-like hepatic disorders fostered by the proin-
flammatory effects of estrogen, and hepatocellular carcinoma,
polyneuritis, Korsakoff syndrome, and dependence).
According to a 2014 meta-analysis, women drinking 75
grams daily of alcohol are 1.5 times more likely to die from
all causes than men for the same level of consumption.34
Alcohol consumption is also socially less well accepted in
women. Fear of stigmatization, sometimes very intense feel-
ings of shame, accompanied by impaired self-esteem, possibly
preexisting anxiety/depression,35 and fear of loss of child cus-
tody all contribute to women waiting longer than men to seek
help.
Cannabis
The acute effects of cannabinoid use may include impairment
of motor coordination, short-term memory, and judgment
(leading to risky behaviors). At high doses, there is a risk of
psychotic disorders (paranoia). Chronic use carries with it a
risk of impaired brain development if used early, amotiva-
tional syndrome, and school problems. The earlier the onset
of use and the more regular it is, the greater the risk of anx-
iety/depression, psychotic disorders (including schizophre-
nia), and dependence.36
Cannabis use may serve specific functions, particularly in
pregnant women, including reducing anxiety or stress and re-
lieving nausea.19,37
Cocaine, Crack, and Amphetamines
Cocaine exerts a powerful psychostimulant effect, inducing a
sensation of intellectual and physical power and indifference
S19

to fatigue, coupled with a feeling of euphoria. These effects,
sought by users, are followed by a “comedown” phase, marked
by depressive-type symptoms, anxiety, and severe irritability.
Cocaine causes strong psychological dependence leading to
irrepressible urges to consume it (cravings), which can occur
shortly or long after the last dose. Chronic consumption is
accompanied by an anorectic syndrome and mood disorders
(excitement, insomnia, depression, anxiety, phobic disorders,
and acute delusional states), and even seizures. Its use can be
responsible for cardiovascular disorders due to vasoconstric-
tion such as hypertension, myocardial infarction, cardiac ar-
rhythmias, and stroke, as well as neurological disorders (con-
vulsive seizures). Nasal inhalation (snorting or sniffing) of co-
caine causes damage to the nasal septum. Injection can lead
to infections due to poor hygiene or sharing of parapherna-
lia. The use of crack (or freebasing) exacerbates psychologi-
cal problems and causes pulmonary effects (cough, bronchi-
olitis, pulmonary arterial hypertension, and acute pulmonary
edema).
Use in combination with tobacco and especially with al-
cohol can also worsen the effects, and particularly the car-
diotoxic effects, of cocaine. The combination of alcohol and
cocaine is metabolized to cocaethylene, which prolongs the
duration of cocaine’s effects, eases the comedown, and in-
creases cardiovascular toxicity.38
Amphetamines are potent psychostimulants and appetite
suppressants. They produce a feeling of euphoria and intense
concentration, giving the user a sensation of increased self-
confidence. They facilitate communication and contact with
others. Acute use can lead to spatiotemporal disorientation,
anxiety attacks, and hallucinations. Physically, use produces
hypertonia and cardiovascular problems (hypertension, in-
creased risk of infarction). After use, there is a comedown
phase with feelings of physical and mental exhaustion and
insomnia.39
Opioids
Users seek a state of calm, well-being, and even euphoria
associated with potent anxiolytic and antidepressant effects.
Heroin causes drowsiness and a slowed heartbeat. The use of
heroin and other opioids (codeine, morphine, tramadol, etc.)
causes very strong physical and psychological dependence.
The risks of overdose are increased when used in combina-
tion with other substances (alcohol, benzodiazepines, etc.).
Abrupt discontinuation causes severe withdrawal. Sharing of
paraphernalia (for injection or sniffing) increases the risk of
infection (HIV, hepatitis B and C). Replacement therapies
(methadone and buprenorphine) with longer half-lives enable
a more peaceful daily life and have little impact on health.40
Specifics affecting contraception and sex life
In 2016, a French study revealed that women who used
cannabis or intravenous/intranasal drugs during life had a
higher probability of using emergency contraception (OR
ranging from 2.20 to 2.90) and experiencing sexual violence
(ORs ranging from 1.87 to 3.14). They also had more sexual
partners than other women, but did not differ in terms of con-
traception. For cannabis specifically, lifetime use was associ-
S20
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ated with an excess risk in the previous 5 years of unplanned
pregnancy (OR, 1.61; 95% CI, 1.00-2.58) and induced abortion
(1.77; 95% CI, 1.26-2.49).41
In 2015, a large retrospective cohort study of 7805 women
found that women with opioid addiction were less likely to use
contraception than other women (56% vs. 81%). In addition,
only 7.4% of them were users of a very effective method (IUD,
implant, or female sterilization).42
Risks for the couple’s fertility
Alcohol
Alcohol is likely to affect male fertility via various mecha-
nisms: decreased testosterone, lower seminal volume and
sperm concentration, impaired sperm motility and mor-
phology, Sertoli cell apoptosis, nuclear abnormalities, and
biochemical and epigenetic impairment of sperm DNA and
RNA.43–47
Alcohol can affect female fertility via hypothala-
mic/pituitary disorders responsible for changes in the
menstrual cycle. According to a 2016 study involving more
than 6000 Danish women aged 21 to 45 years, drinking more
than 14 glasses of alcohol per week, compared with abstinence,
was associated with an 18% decrease in expected fertility.48
Other substances
Regardless of the PS, studies agree that fertility decreases
in both men and women through impairment of the
hypothalamic–pituitary–gonadal axis (cannabis, opi-
ates/ORT) and an increase in prolactin levels (cannabis,
cocaine, opiates, ORT). Nuclear damage and tubular degen-
eration have also been described in rats treated with MDMA.
Tetrahydrocannabinol (THC) has an inhibitory effect on
folliculogenesis, fertilization, tubal migration, egg implanta-
tion, and continuation of pregnancy.49–51 Regular heroin use
leads to amenorrhea, and early signs of pregnancy may be
interpreted as signs of withdrawal, sometimes leading to a
very late diagnosis of pregnancy.52–55 (See Table, Appendix 1.)
Risks for the pregnancy
Alcohol during pregnancy
In vitro, short and acute ethanol exposure in the first
trimester negatively affects placental cell growth. In rats, dose-
dependent prenatal exposure compromises growth and pla-
centation via impairment of morphogenesis in the chorionic
villi, a decreased number of invasive precursor cells, and in-
hibition of trophoblast cell adhesion and motility.56,57 Studies
in women show excess placental implantation abnormalities
such as placenta accreta (OR, 3.10; 95% CI, 1.69-5.44).58
All of these morphogenetic abnormalities as well as dose-
dependent placental vasoconstriction increase the risk of mis-
carriage or stillbirth, bleeding, preterm birth, gestational hy-
pertension, fetal or intrauterine growth restriction, and pre-
mature rupture of membranes (PROM). Compared with non-
drinkers, the risk of placental vascular dysfunction in women
who drank at least 5 alcoholic beverages per week was twice
as high, while women who consumed 1 to 2 drinks per week
had an increased risk of only 9%.59
Volume 67, No. S1, November/December 2022

A 2014 study confirmed this increased risk of miscarriage
(OR, 1.19; 95% CI, 1.12-1.18.60 A 2019 systematic review cou-
pled with a meta-analysis found an association between ma-
ternal alcohol consumption and a small-for-gestational-age
newborn as well as risk of low birth weight.61
Children of mothers who continued to drink during preg-
nancy had a lower birth weight than those of mothers who
decreased their consumption.62
Cannabis during Pregnancy
The 2 main cannabinoids studied, delta-9-
tetrahydrocannabinol (THC) and cannabidiol (CBD), activate
2 types of receptors. One of these is CB1R, which is widely ex-
pressed in the central nervous system and peripheral tissues,
including uterine smooth muscles and the placenta. THC
crosses the placental barrier very easily. Typically smoked in
France, its specific toxicity combines with that of tobacco. The
risks are associated with both the decrease in oxygenation
induced by CO poisoning when cannabis, like tobacco, is
smoked, and THC’s specific pharmacological action.
Stimulation of placental CB1R receptors inhibits cy-
totrophoblast proliferation. Cannabis use is implicated in
implantation difficulties and placental hypoperfusion, with
an increased risk of placenta previa and spontaneous
miscarriage.63,64 A recent cross-sectional study showed that
cannabis use increases the risk of a low birth weight newborn
by 50%, regardless of maternal age, geographic origin, level of
education, or tobacco use (OR, 1.5; 95% CI, 1.1-2.1).65 While
a retrospective cohort study by Corsi et al. of 9247 women
users found a statistically significant excess risk of preterm
birth (RR, 1.41; 95% CI, 1.36-1.47), Crume et al. did not find
such an association after adjustment for tobacco use.21,65
Psychostimulants: cocaine, crack, and amphetamines during pregnancy
Pregnant women who use cocaine are more likely to have low
weight gain, cardiac complications (hypertension, arrhyth-
mia, cardiac ischemia, or hemorrhagic stroke), and an in-
creased risk of preeclampsia (RR, 1.73; 95% CI, 1.77-2.5).66
Thus, during acute intoxication, pregnant women may present
a clinical picture combining hypertension and tachycardia.
This can mimic eclampsia, which should thus be ruled out by
laboratory tests.67
Cocaine use in the first trimester increases the risk of
miscarriage, independently of other risk factors, including
tobacco.68,69 The risk of developing placenta previa is 2 to 4
times higher, although it cannot be distinguished from the
risk due to tobacco.70–72 A meta-analysis also showed a sig-
nificant increase in the incidence of placental abruption in
all groups of cocaine users, with or without other substances,
compared with non-users or users of multiple drugs excluding
cocaine.73,74
Placental vasoconstriction and decreased uterine flow
caused by cocaine use affects maternal-fetal exchanges, induc-
ing a significant increase in the risk of preterm birth (OR,
2.22; 95% CI, 1.59-3.10), a decrease in head circumference of
-1.65-cm (95% CI, -3.12 to -0.19 cm), and excess risks of small-
for-gestational-age birth (OR, 4.00; 95% CI, 1.74-9.18) and low
birth weight (OR, 2.80; 95% CI, 2.39-3.27).66,72,74
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Opioids, opiates, and ORT during pregnancy
In 2019, the French referral center for teratogenic agents
(CRAT) reported that tramadol is found in the fetal circula-
tion at concentrations equivalent to that in maternal plasma.75
Women who are chronic opioid and ORT users typically ex-
perience hyperalgesia (increased sensitivity to pain) and tol-
erance requiring higher doses of opioid agonist drugs dur-
ing labor, while giving birth, and during the postpartum pe-
riod. Opiates with μ-agonist properties such as nalbuphine
(Nubain) and μ-receptor antagonists (naloxone) can precipi-
tate acute withdrawal syndrome in ORT users (LE ).76–79
Methadone decreases the basal fetal heart rate and its vari-
ability and accelerations. Buprenorphine has the same effects
but to a lesser extent.80,81 No solid evidence supports an as-
sociation between fetal growth restriction and ORT use.82 A
US cross-sectional study of 138,224 pregnant users between
1998 and 2009 found an increased prevalence of depression,
anxiety, and chronic health problems. After adjustment, there
was an increased risk of preterm birth, fetal growth restric-
tion, and stillbirth. After giving birth, drug users experienced
postpartum depression 10 times more often than nonusers.31
Embryo/Fetal Effects
Alcohol
Ethanol is a small hydrophilic, lipophilic molecule that rapidly
diffuses through the placenta. Enzymatic detoxification oc-
curs only in small quantities after the second trimester of preg-
nancy, and the fetus is able to ingest the ethanol present in the
amniotic fluid. As a result, the alcohol concentration in the
fetus is higher than in the mother.83
The harmful effects of prenatal alcohol exposure are ex-
erted via various mechanisms: (1) teratogenic effects: linked
to ethyl alcohol or ethanol and its catabolite, acetaldehyde,
causing malformations that can affect all organs83 ; (2) neuro-
toxic effects: increased neuronal apoptosis, inflammatory dis-
orders, and neurotransmitter abnormalities; (3) vascular ef-
fects: brain angiogenesis disorders84 ; and (4) epigenetic ef-
fects: changes in the expression of genes involved in placental
and embryonic/fetal growth,85 morphogenesis, neurogenesis,
and neuronal migration.86–90
Exposure-Dependent Risks
• Preconception exposure
Use before conception induces epigenetic abnormalities
in the sperm. These are responsible for disrupting the expres-
sion of genes involved in the regulation of cell proliferation,
embryonic/placental growth, and fetal brain development and
result in a phenotype equivalent to fetal alcohol syndrome
(FAS).91–93
A meta-analysis published in 2020 examined the role of
preconception alcohol use in men, using data from 55 stud-
ies in 41,747 babies with congenital heart disease. It reports
that paternal alcohol consumption in the 3 months before
conception is associated with a 44% increase in the infant’s
risk of congenital heart disease. Occasional, excessive alco-
hol consumption (ie, binge drinking) is associated with a 52%
increase in the probability of a congenital heart defect. The
S21

authors recommend discontinuing all alcohol consumption at
least 6 months before fertilization.94
• Early exposure through the 5th week after the last men-
strual period (3rd week of pregnancy)
While women are usually unaware of pregnancy at this
early stage, there is a major risk with respect to implantation
(risk of placenta accreta, lack of trophoblast invasion) and pla-
cental development (histologic disturbances with a reduced
number and size of the villi and thus a decrease in placental
exchanges).56–58
Administration of alcohol to pregnant mice during the
preimplantation period affects subsequent fetal develop-
ment and causes a phenotype similar to FAS, including
growth restriction, craniofacial abnormalities, and increased
mortality.95 Early exposure leads to placental demethylation
of paternal alleles of the H and Igf genes involved in pla-
cental and embryonic growth.96
• Exposure 5 to 12 weeks after the last menstrual period
The risk of malformation is greatest during this period of
embryogenesis. The teratogenic molecule that is alcohol dis-
rupts the development of various organs (face, extremities,
and internal organs) in a specific chronological pattern via
several mechanisms including increased apoptosis, early vas-
cularization abnormalities, and epigenetic changes in the ex-
pression of certain genes crucial for embryo formation.86
In 1968, French pediatrician Paul Lemoine and his col-
leagues provided the first complete clinical picture97 of this
pattern of malformation in the offspring of mothers with
chronic alcoholism, and Jones and Smith introduced the term
“fetal alcohol syndrome (FAS)” in 1973.98 It refers to intrauter-
ine growth retardation in alcohol-exposed children, classically
with microcephaly, characteristic facial dysmorphism (nar-
row palpebral fissures, long, smooth, rounded philtrum, thin
upper lip with poorly defined Cupid’s bow), malformations,
and neurocognitive and behavioral disorders.99,100
• Exposure from 12 weeks after the last menstrual period
This type of exposure does not pose a risk of visceral or fa-
cial malformations. Growth restriction may be present due to
placental vasoconstriction. The major risk is neurocognitive
and behavioral: morphogenesis, histogenesis in the brain, and
construction of neural circuits occur throughout pregnancy
and come to an end only in young adulthood, at around 25
years of age. Some of these mechanisms also exhibit epigenetic
determinism.90
Risks depend on amount and duration of use
The greater the quantity of alcohol and the more numer-
ous the episodes of binge drinking, the more frequently dys-
morphism and cognitive/behavioral disorders (especially low
nonverbal IQ and attention disorders) are reported. The oc-
currence of fetal alcohol spectrum disorder (FASD) is higher
by a factor of 12 when alcohol is consumed in the first
trimester (P <.001), a factor of 61 when consumed in both the
first and second trimesters, and a factor of 65 when consumed
during all 3 trimesters.101
One of the most hotly debated issues concerns the impact
of low consumption. A recent study shows that the typical fa-
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cial dysmorphism is 2.5 times more common in children with
even one exposure, compared with children with no exposure,
and higher by a factor of 8.5 in children exposed to an average
of 1–4 drinks per week.102
On the cognitive side, a series of articles published in 2012
found no neuropsychological disorders with low to moderate
weekly alcohol consumption early in pregnancy.103,104 How-
ever, Astley and Grant, among others, cast doubt on these re-
sults; it seemed premature to examine the full impact of ex-
posure on the performance of complex tasks by children aged
only 5 years.105
The type of consumption can also modulate the effects in
children. Simultaneous consumption of several drinks in the
same day seems to account for more significant consequences
than consumption split over several days and thus indicates
that binge drinking is an additional risk factor.106
Genetic makeup-dependent risks
The effects of drinking during pregnancy on the unborn
child are also modulated by both maternal and fetal ability
to eliminate alcohol via genetic polymorphisms of alcohol
dehydrogenase.107
Cannabis
While THC readily crosses the placenta, there have been few
studies on its distribution to the fetus and resulting effects, and
their results are conflicting. While some studies find no risk of
malformation,51,63 others report a twofold risk of gastroschi-
sis malformations or abnormality of the ventricular septum
after exposure in the first trimester via a possible vascular-
disrupting effect.108,109
In mice, administration of the synthetic cannabinoid CP
99,540 at an early stage of pregnancy (neurulation), which
usually occurs in humans before pregnancy is recognized,
has been shown to be teratogenic (anencephaly, holoprosen-
cephaly, cortical dysplasia, microphthalmia, iris coloboma, fa-
cial clefts, and cleft palate) at doses that are low but equivalent
to potential human exposure, with a dose effect and possible
potentiation by an alcohol effect.110,111
Cocaine and amphetamines
In vivo studies in animals show that cocaine crosses the pla-
centa rapidly, by simple diffusion.112 A review found no in-
creased malformation risk in embryos exposed to cocaine
or methamphetamine.113 In a subsequent cohort study, Huy-
brechts et al. identified a moderately higher adjusted relative
risk of heart defects with maternal methylphenidate use (RR,
1.28; 95% CI, 0.94-1.74) not found with amphetamines (RR,
0.96; 95% CI, 0.78-1.19).114
Heroine and ORT
Consumption of opioids and ORT did not seem to increase
the risk of congenital malformation.115,116
Effects on the newborn
With PS use during pregnancy and through birth, the new-
born may present floppy infant syndrome for the first few days
Volume 67, No. S1, November/December 2022

followed by neonatal abstinence syndrome (NAS) combin-
ing extreme irritability, trembling, incessant crying, seizures,
sleep problems, feeding disorders with decreased sucking re-
flex, digestive disorders with diarrhea, and irregularities in
heart and respiratory rates. Use of multiple substances during
pregnancy increases these symptoms.116
Alcohol
Manifestations at birth reflect recent exposure in the days pre-
ceding childbirth. In the first 12 hours of life, the newborn can
present floppy infant syndrome with a combination of drowsi-
ness, hypotonia, and feeding disorders. Secondarily, after 12
hours, the risk of withdrawal syndrome is significant.116
Cannabis
A few small cohort studies in the 1980s and 1990s reported
neurologic behavioral changes in babies (prolonged star-
tle reflexes, high pitched crying, and abnormal EEG sleep
cycles).117,118 In their retrospective cohort study, Corsi et al.
found an excess risk of a 5-minute Apgar score < 4 (RR,
1.28; 95% CI, 1.13-1.45) and transfer to neonatal special or
intensive care (RR, 1.40; 95% CI, 1.36-1.44).21 Prospective
longitudinal studies have not reported an increased risk of
neonatal cannabis withdrawal.119 In a recent prospective co-
hort study, neonates exposed to combined cannabis and to-
bacco use, compared with those exposed to tobacco alone,
manifested significantly poorer self-regulation and attention,
greater lethargy, and an increased need to be held in the first
few minutes of life.120
Cocaine and amphetamines
Newborns exposed to cocaine in utero present trembling, high
pitched crying, irritability, excessive sucking, and hyperactiv-
ity more often than unexposed babies.74 The meta-analysis
by Held of children of mothers who use substances (cocaine
only or multidrug users) examined 7 cognitive domains with
the Neonatal Behavioral Assessment Scale (NBAS). While
neonates exposed to cocaine have abnormal reflexes and lower
scores for habituation, orientation, motor performance, auto-
nomic regulation, and abnormal reflexes at birth, their results
3 to 4 weeks after birth were the same as those of unexposed
newborns.121
Health Canada states that the clinical signs of neona-
tal methamphetamine withdrawal are nonspecific: irritabil-
ity, hypertonia, and poor sucking.122 A prospective controlled
longitudinal study using the NBAS scale showed that new-
borns exposed to methamphetamine in utero presented dis-
organized waking and sleep states, poorer quality movements,
and increased stress behaviors,123 but that these symptoms
were not observed beyond the first month.124
Opiates
The opioid withdrawal syndrome was first described in the
1950s. Its symptoms include neurologic, digestive, respira-
tory, and vegetative signs. It may occur with exposure to
heroin or ORT in about 40–60% of cases in the first few
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days of life. It can be assessed by the Finnegan or Leipzig
score and may require morphine treatment if nursing care is
insufficient.125
Studies by the French Pregnancy and Addiction Study
Group (GEGA) in 2015 and by Jones in 2010 found no sig-
nificant difference in the frequency of NAS for 2 replace-
ment therapies, methadone and buprenorphine.116,126 A meta-
analysis of 10 studies, 5 prospective and 5 retrospective,
also showed no relation between maternal methadone or
buprenorphine dosage and NAS.127 A cohort study involving
822 newborns who had had NAS showed that benzodiazepine
use in mothers taking buprenorphine or methadone was as-
sociated with an increased risk of developing withdrawal syn-
drome requiring pharmacological treatment (risk ratio, 1.51;
95% CI 1.04–2.21), a result not found for the association of to-
bacco, marijuana, cocaine, gabapentin, or selective serotonin
reuptake inhibitor with opioid use.128
Opiates such as tramadol and codeine are likely to induce
NAS in babies even at therapeutic doses.75
Parental presence and breastfeeding decrease the severity
and duration of the withdrawal syndrome, with any necessary
drug treatments.129
Effects on breastfeeding
This issue cannot be limited to its pharmacological aspects
(passage into breast milk and digestive absorption by the
child). A key factor is the parental environment, such as the
mother’s willingness to maintain closeness and pay attention
to the child.
Alcohol
Ingested alcohol passes quickly into breast milk. The peak
level in breast milk is observed after 30 to 60 minutes if the
alcohol is consumed on an empty stomach, and after 60 to
90 minutes if drunk with food. Alcohol does not accumulate
in breast milk. Breast milk contains alcohol at levels similar
to maternal blood, and the drop in level in the milk paral-
lels that in serum (ie, about 0.15 g/L/h). To eliminate all traces
of alcohol from her breast milk, a woman 1.6 m/5’3" tall and
weighing 62 kg/137 lb would have to wait 2 hours 20 min-
utes after consuming one standard drink and 9.5 hours after
4 drinks.
While alcohol concentrations in the mother’s blood and
breast milk are similar, concentrations in the infant’s blood
will be very different, as they ingests only 5% to 6% of the
weight-adjusted alcohol dose ingested by the mother, due to
the infant’s digestive filtration.13
Contrary to popular belief, alcohol consumption is not
beneficial for breastfeeding. While the beta-glucan content in
beer does increase human milk production, alcohol blocks
the ejection reflex, causing a temporary decrease in milk pro-
duction. Consuming 2 standard drinks causes a 20% reduc-
tion in milk production or even cessation if those 2 drinks are
consumed regularly. There is a dose effect and interindividual
variability.13
Data remain sparse about the long-term effects in chil-
dren breastfed by mothers who consume alcohol. An Aus-
tralian prospective cohort study evaluated breastfed infants,
S23

at 8 weeks and then 12 months of life, for social, mental, and
motor development. The alcohol consumption of most of the
mothers was considered moderate and almost always timed
to minimize the amount of alcohol in the milk. The infants
of mothers who drank alcohol after childbirth had no more
adverse effects at 12 months than infants of non-drinking
mothers.130
A large, longer-term Australian case-control study found
that (self-reported) maternal alcohol consumption during
breastfeeding was associated with a dose-dependent decrease
in nonverbal reasoning in children aged 6–7 years. However,
that correlation was no longer statistically significant in 8 to
11-year-olds.131 In a follow-up study, a dose-dependent associ-
ation was found between higher maternal alcohol consump-
tion during breastfeeding and poorer scholastic performance
in children aged 3 and 5 years,132 but no cognitive/behavioral
problems were identified at either 6 to 7 years or 10 to 11
years.133
Cannabis
THC passes into human milk. Pharmacological studies con-
ducted in a cohort of California women, most of whom in-
haled cannabis smoke, found that THC concentrations var-
ied according to frequency of use and the time between use
and testing. THC persists in human milk for up to 6 days after
use.134
The insufficient methodology of studies dating from 1985
to 1990 (insufficient allowance for confounding variables, no
long-term follow-up) currently makes it impossible to con-
firm or rule out effects in children.135 No risk/benefit studies
have yet been performed.
Cocaine and crack
When used, cocaine and its metabolites are detectable in hu-
man milk at widely varying concentrations.136,137 If contami-
nated milk is ingested, the infant’s urine remains positive for at
least 60 hours.138 These effects can be severe, with irritability,
seizures, hypertension, and tachycardia or even cardiogenic
shock.137
Methamphetamine and amphetamines
Methamphetamine and its metabolites are detected in hu-
man milk for up to 100 hours after use by the mother. Am-
phetamines become concentrated in this milk (milk/plasma
ratio 2.8 to 7.2) and can cause irritability, nervousness, and
insomnia.
There are no available data to prove or rule out a possible
methamphetamine risk in breast-fed children.137
Opiates
When street heroin is used, the types of substances used to
cut it are unknown, and it cannot be known if they pass
into human milk.139 When replacement therapy is used, the
quantity of methadone or buprenorphine ingested via the
milk is low, on the order of 3% of the maternal dose for
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methadone and 1% for buprenorphine. When tramadol is
taken, the breast-fed child receives about 3% of the maternal
dose. No specific events have been reported to date in breast-
fed children.75,139,140
Breastfeeding decreases the duration and severity of the
child’s withdrawal syndrome, probably more due to mother-
ing skills than as a result of the passage of substances into
women’s own milk.141,142
Risk of sudden unexpected infant death
Due to the many confounding variables, the probative scien-
tific evidence is contradictory and insufficient. Increased risk
of sudden unexpected infant death (SUID) should be consid-
ered in light of the general context, including lifestyle and in
utero exposure to toxic substances.
Alcohol
Prenatal alcohol exposure affects the maturity and function-
ing of the autonomic nervous system, particularly reflecting
reduced parasympathetic activity and exposure. This impair-
ment of the autonomic nervous system accounts for the in-
creased risk of SUID, which is also potentiated by tobacco
use in combination with alcohol. SUID risk is thus higher
by a factor of 11.79 in infants whose mothers reported both
drinking and smoking beyond the first trimester, vs a factor of
3.95 for alcohol consumption alone beyond the first trimester
and a factor of 4.86 for smoking alone beyond the first
trimester.143
Cannabis
In their case-control study published in 2001, Scragg et al. re-
ported an increased risk of SUID when cannabis was smoked
during pregnancy (OR, 1.60; 95% CI, 1.13, 2.27) or at least once
a week after birth (OR, 1.73; 95% CI, 1.23, 2.43), after adjust-
ment for daily tobacco smoking.144 Klonoff-Cohen identified
a significantly higher risk of SUID (OR, 2.2; 95% CI, 1.2-4.2)
when fathers used it at the time of conception, but not when
mothers used it during pregnancy.145
Cocaine
A 1997 meta-analysis by Fares et al. found a statistically sig-
nificant risk of SUID in infants of women cocaine users
vs the drug-free group (OR, 4.1; 95% CI, 3.2-5.3), but
not compared with the other/multiple-drug group (OR,
2.7; 95% CI 0.9-8.2).146 They concluded that the increased
risk of SUID alone cannot be specifically attributed to in
utero cocaine exposure alone, but only to exposure to all
substances.
Opiates
Epidemiologic studies in the 1990s showed a level of SUID
about 5 times higher in children exposed to opiates in utero.
The rate increased from 1.39 to 5.83 per 1000 opiate-exposed
Volume 67, No. S1, November/December 2022

children, with an OR of 3.2 for methadone and heroin (95%
CI, 1.2–8.6).147–149
Risks for child development
Alcohol
In addition to the long-term physical repercussions (growth
disorders, physical, esthetic, and functional effects of malfor-
mations) of FAS, prenatal alcohol exposure is responsible for
neurocognitive and behavioral disorders.150–152
Even moderate exposure can cause neurologic damage,
which then can then appear in infants, but also in children,
adolescents, and adults. While FAS is the most visible manifes-
tation of the effects of prenatal alcohol exposure, FASD refers
to an entire series of disorders in individuals with or with-
out facial dysmorphism and malformations.151,153–155 Thus, any
alcohol consumption can have neuroanatomical and cogni-
tive/behavioral effects. In addition to microcephaly, magnetic
resonance imaging may reveal abnormalities of the corpus cal-
losum, cerebellum, and hippocampus, as well as neuronal mi-
gration and gray matter volume disorders (cingulate gyrus,
medial-frontal gyrus, and caudate nuclei).156–158 The func-
tional effects vary: psychomotor delay, neurocognitive and
behavioral disorders appearing in children and even adults
(learning difficulties, memory deficit, decreased verbal flu-
ency, executive function disorders, psychobehavioral and psy-
choaffective disorders, attention-deficit/hyperactivity disor-
der) responsible for personal, interpersonal, scholastic, social,
and professional dysfunction.106,152,154,155,159–167
From an epidemiologic perspective, FASD is the most
common cause of cognitive impairment in North America,
ahead of Down syndrome and cerebral palsy.162 A 2017 review
of the literature between 1973 and 2015 by Popova et al. re-
ported a global prevalence of FAS of 14.6 per 10,000 popula-
tion (95% CI, 9.4-23.3).168
There are few studies in France. In 2018, Santé Publique
France’s FASD surveillance report analyzing data from com-
puterized medical records in France between 2006 and 2014
showed a reported prevalence of FASD of 0.48 case per 1000
births, including 0.07 case of FAS per 1000 births, but also
significant regional disparities. The region with the highest
prevalence was Reunion Island (1.22 per 1000).169 These re-
sults nonetheless underestimate the prevalence of FASD, par-
ticularly because of the difficulty in identifying children with
such disorders and the lack of data beyond the neonatal pe-
riod.
It is generally estimated that FASD in France affects at least
1% of births, around 8000 babies per year. This implies that
nearly 500,000 French people are affected to varying degrees
by fetal alcohol exposure. Alcohol consumption during preg-
nancy is thus the leading cause of nongenetic mental retar-
dation and social maladjustment of children in France, and it
is preventable. Its cost to society is significant, estimated at a
lifetime average of 1.3 million euros.170,171
Cannabis
In mice, repeated and extensive activation of CB1Rs at sen-
sitive brain development periods affects the expression and
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function of insulin-like growth factor and the fetal neuro-
transmitter system, which is involved in higher cognitive
functions.172
Possible positive associations have been found between
behavioral disorders and prenatal maternal cannabis use
(beta, 0.27; 95% CI, 0.02-0.52), as well as preconception
cannabis exposure (beta, 0.53; 95% CI, 0.29-0.77).173
These effects in children can persist in the form of sleep
disturbances for up to 3 to 4 years.174 Key long-term follow-
up data show that neither growth nor intellectual abilities,
as measured by the child’s IQ, are disturbed, but that learn-
ing difficulties related to cognitive and behavioral disorders
occur. These children have more symptoms of hyperactiv-
ity and impaired attention, memory, reasoning, and abstrac-
tion (mathematics) — difficulties that are sources of academic
failure. Beginning in preadolescence, they are also reported
to have anxiety and depression more frequently.175–179 An ac-
tivity imbalance in the dorsolateral prefrontal cortex, rich in
cannabinoid receptors, involved in executive functions (ab-
straction, reasoning, decision making, etc.) has been demon-
strated in young people 18–22 years of age exposed in utero to
cannabis.180
Cocaine
No specific morphologic component of prenatal cocaine ex-
posure has been identified in long-term studies.181,182 The
negative impact on growth persists beyond infancy, even af-
ter adjustment for confounding factors, particularly on the
weight/height ratio, especially through 10 years of age.182–184
Children born at term and thus with the greatest exposure
to cocaine, associated with early undernutrition, had a higher
body mass index at 9 years of age.185
A systematic review of the literature analyzed the ef-
fects on cognitive level, motor performance, and behavior in
children.67 No significant difference in cognitive level was
found among the 4 exposed/unexposed studies, but there was
a tendency toward lower IQ in exposed children and learn-
ing difficulties in 3 studies. Studies involving motor perfor-
mance are conflicting. Most did not identify any increased im-
pairment, but 2 studies showed poorer performance with very
high exposure. For behavior, 2 exposed/unexposed studies
found no difference, while a subsequent study identified more
frequent oppositional and attention deficit/hyperactivity dis-
orders in exposed children.186 Impairment has also been ob-
served in cognitive control via impairment of brain func-
tion in the frontoparietal areas involved in decision-making
processes.187 Nevertheless, in all of these studies, environ-
mental factors (particularly, placement of children exposed in
utero to cocaine in foster or adoptive families) seem to play an
important role in the deterioration, maintenance, or improve-
ment of behavior in exposed children.181–187
Amphetamines
Children exposed to amphetamines show greater anxi-
ety, depression, emotional dysregulation, and externalized
attention-deficit/hyperactivity-type disorders than their non-
exposed counterparts.124
S25

Opiates
Many studies have found no difference in cognitive de-
velopment after correcting for biases related to socioeco-
nomic conditions.188–195 A large meta-analysis comparing
1455 opiate-exposed children with 2982 unexposed identified
lower performance levels on motor and cognitive develop-
ment scales in exposed children at 0–2 and 3–6 years of age.
It is noteworthy, however, that the difference was no longer
statistically significant in young people 7 to 18 years old.196
Maternal opioid use and NAS are associated with de-
terminants of impaired mental health in children.197 More
specifically, Uebel et al. demonstrated in an Australian co-
hort that children with a history of NAS were significantly
more likely to be hospitalized for cognitive impairments
(OR, 2.8), psychological disorders (OR, 2.9, including speech
and language disorders, OR, 3.6), autism spectrum disor-
ders (OR, 3.6), and behavioral and especially emotional con-
trol disorders (OR, 4.1).198 The etiology of these disorders
is still unclear. However, it is recognized that stress can im-
pact developing cortical structures, particularly in areas of
the brain involved in social behavior and anxiety, such as
the parahippocampal gyrus and the middle temporal gyrus,
respectively.199,200
SCREENING AND RECOMMENDED MANAGEMENT
Addressing psychoactive substance use with women and
their partners
The more professionals systematically address the topic of
consumption, the more appropriate their speech will be and
the more confidence patients will have talking about it. To feel
comfortable, these professionals must anticipate positive re-
sponses, know how to respond to patients (about effects on
pregnancy and what to do about them), and know the profes-
sionals to whom they can be referred.
Questions should be simple, with no moral connotations.
Professionals should introduce PS as a natural topic of the
appointment. It can make things easier to point out that all
women are asked these questions, to put up posters, and to
provide leaflets in the waiting room (expert consensus).
Some sample questions include: (1) Have you used psy-
choactive substances in the past few months? Tranquilizers,
sleeping pills? Pain medications (codeine, tramadol, Lama-
line, etc.)? (2) Would you say that when you drink alcohol, it’s
more often wine, beer, rum…? (3) Do you smoke? What do
you smoke? Factory-made or roll-your-own cigarettes? Some-
thing else? Do you sometimes smoke cannabis? (4) What can
you tell me about your alcoholic beverage consumption in the
past few months? Before your pregnancy? (5) When you are
stressed out or anxious, how do you cope? (6) When was the
last time you had a glass of alcohol, beer, or wine?
Assessment for action
PS use must be accurately entered in the medical record. It is
important to enter all consumption, however low; this helps
both to verify that the subject has already been discussed and
to assess any changes in it (see Box 1).
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To evaluate alcohol consumption and enter it in the pa-
tient’s file, it is necessary to understand the concept of a stan-
dard drink (see Figure 1).
When taking the history, it is preferable to discuss PS use
after the medical and surgical history, once a relationship of
trust has been established. All pregnant women should be
asked about their substance use, including during the period
around conception. It is advisable to evaluate all substance use
by pregnant women at each appointment, before giving ad-
vice on abstinence. It is advisable to ask about the partner’s
substance use (expert consensus for each of these recommen-
dations).
Although women from all walks of life are affected, it is
essential to pay particular attention to those who present risk
factors for greater use: (1) environmental factors: low income,
insecurity, isolation, urban living, partner who uses PS, violent
partner, family conflicts; (2) individual factors: young woman,
student, single, with a personality disorder, anxiety or mood
disorder, low self-esteem, history of childhood trauma, sexual
violence, delinquency.
The personal and environmental situation, needs, and re-
sources of the woman (couple) should be assessed. Early pre-
natal care, which has become compulsory for all pregnant
women in France, makes it possible to examine them in depth
and to offer them appropriate support.
The “vulnerability/addiction” self-administered ques-
tionnaires developed by some teams, such as that from the
Pregnancy and Addiction Study Group (GEGA) in France,
can help identify factors associated with substance use (http:
//www.asso-gega.org/auto-questionnaire22.htm).
If the situation is simple, the professional can perform a
brief intervention and continue to see the patient alone. If
there is at least one unfavorable element, the situation is con-
sidered complex and will require personalized, coordinated
networking throughout the pregnancy and after birth.
Although there is no validated French questionnaire for
screening for PS use during pregnancy, those developed for
the general population can be used. By assessing harmful
habits and dependence, they help identify which patients may
respond favorably to a brief intervention performed by the
primary care professional and those whom it is advisable to
refer to an addiction professional. The brief intervention in-
volves collecting information on the reported substance use
and then providing her with information about the substance
use assessment results and the correlation between substance
use and effects, and finally to ask the user if she plans to reduce
her use and how she plans to do so.
Outside of pregnancy, a referral to an addiction profes-
sional should be offered to women with a harmful habit, that
is, (1) for alcohol, more than 2 drinks daily and/or binge drink-
ing more than 5 standard drinks at least once a week; (2) for
cannabis, one joint daily and/or more than 4 joints per occa-
sion; (3) for heroin or cocaine: any use at all.
Moreover, this referral should be offered to any pregnant
woman who continues her PS use after discovery of preg-
nancy, regardless of the amount and frequency.
Addresses and additional information can generally be
obtained from public health authorities or associated. In
France, the following toll-free numbers are useful: Drogues
Info Service (0 800 23 13 13) or Écoute Alcool (0 811 91 30 30),
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Figure 1. What is a standard drink? Reprinted with permission. Source: alcool-info-service, Santé Publique France (https://www.alcool-
info-service.fr/alcool/boissons-alcoolisees/verre-alcool)

Table 2. Classification of situations based on contextual factors

Simple situation*
Favorable factors
Use Occasional
Method of use Minimal
Quitting history Success or period of
abstinence
Social/family problems None or moderate
Psychological context No current problem or
history
Multiple substances No
Health Regular health care, no or
few health problems
Obstetric context Early discovery of
pregnancy, regular care
∗
Source: Réseau de Périnatalité Occitanie data
Complex situation*
Unfavorable factors (at least )
Regular
Significant occasional alcoholism (binge drinking, getting high, use as
anxiolytic, antidepressant, sleep aid, stimulant)
Never succeeded or quickly resumed
Significant, chronic
Partner or co-parent is a user
Emotional fragility, difficulty managing emotions, personality
disorders, history of anxiety/depression or trauma, etc.
Yes
No health care or multiple irregular health problems
Late discovery of pregnancy, irregular care

Écoute Cannabis (0 811 91 20 20). In addition, information is (expert consensus). It is also advisable to assess the overall
available from the Interministerial Mission on Drug Control situation, the patient’s environment, and her network of pro-
and Addictive Behaviors (MILDECA: https://www.drogues. fessionals before offering additional help (expert consensus).
gouv.fr/la-mildeca/publications).

Situational management
Based on the responses during the various interviews, differ-
ent situations can be identified that will determine the profes-
sional’s approach and recommendations for pregnancy mon-
itoring and specific support.
If the situation is simple (Table 2) and there is low or slight
risk (Table 3 ), the professional can manage the situation alone.
In all other cases, coordinated networking is recommended
Recommendations based on the timing of the
appointment with the patient
Gynecologic or preconception follow-up appointment
1. In the event of PS use by a woman of childbearing age, pro-
vide information to any woman of childbearing age using
PS about the impact of this use on the pregnancy and the
child and advise her to stop PS use. If necessary, offer to

Journal of Midwifery & Women’s Health r www.jmwh.org S27


Table 3. Actions to take in different situations
Situations Type of use and context
Low risk -No psychoactive substance use other than
alcohol or quit > 1 year before pregnancy
-Alcohol consumption less than or equal to
WHO* threshold, quit before pregnancy or
during first three weeks of pregnancy
Slight risk -Stopped using cannabis on discovery of
pregnancy
-History of cocaine, amphetamine, or opiate use,
quit more than one year ago
-Alcohol consumption above WHO* threshold,
quit before 3rd week of pregnancy
Moderate -Alcohol consumption below the WHO*
risk threshold, continuing after 3rd week of
pregnancy
-Cannabis: < 1 joint per day or < 4 joints on 1
occasion, continuing after 3rd week of
pregnancy
-Cocaine, amphetamine, or opiate use in the year
prior to pregnancy
-one single type of substance used other than
tobacco
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Professional’s approach
-Reinforce prevention message during interviews and with the help of
leaflets with a message such as: “It is imperative not to consume
alcohol or other substances during your pregnancy. These
substances are dangerous for you and your unborn baby.” This
message is reiterated at each appointment.
-Regular monitoring and early prenatal care can be provided by a
midwife or a doctor (general practitioner, gynecologist, or
obstetrician-gynecologist) depending on the woman’s preference**
-Regular ultrasound follow-up is suggested.
-Schedule perinatal prevention workup and/or see patient again for
office visit before end of first trimester (ideally within 15 days after
the previous appointment) to inquire about any resumed use and to
deliver prevention messages
-Opinion of an obstetrician-gynecologist for placental risk assessment
and fetal growth monitoring**
-Emphasize importance of early prenatal care
-Offer a referral to an addiction specialist, given the risks of relapse
during pregnancy or the postpartum period
Immediate approach
Schedule a perinatal prevention workup or see patient for an office
visit before end of first trimester (ideally within 15 days after the
previous appointment) to inquire about any resumed use and to
deliver prevention messages
Monitoring of pregnancy**
Pregnancy should be considered a moderate-risk pregnancy
-The opinion of an obstetrician-gynecologist should be requested to
discuss the indication for close obstetric monitoring (risk of
miscarriage, growth retardation, fetal death in utero, gestational
hypertension), and additional ultrasound follow-up.
-Schedule early prenatal care
Management of substance use
-Evaluate the risks (appointment with pediatrician or geneticist if risk
of FASD) and encourage quitting
- Set up appointments for brief interventions and motivational support
Actions to take at delivery
-A neonatal examination should be performed by a professional
trained in FASD and withdrawal syndrome
Breastfeeding
-Breastfeeding should be encouraged, but only after neonatal
reassessment of substance use. A woman who is breastfeeding
should be informed of the benefits to the child of quitting and
should be supported in this process.
(Continued)
Volume 67, No. S1, November/December 2022

Table 3. Actions to take in different situations
Situations Type of use and context
High risk -Consumption of large amounts of alcohol (>
30–40 g per occasion or > 70 g of alcohol per
week) during pregnancy
-History of children with FASD
-Moderate-risk consumption, but in association
with psychiatric disorders or physical/sexual
violence during this pregnancy
-Cannabis: ≥ 1 joint per day or > 7 joints per
week and/or > 4 joints per occasion,
continued after discovery of pregnancy
-Heroin, cocaine: any use during pregnancy
-Multiple substance use (regardless of amounts)
∗
WHO threshold: < 2 drinks per day and less than 10 drinks per week
∗∗
Follow-up and referral of pregnant women201
refer her to a specialist. If she does not plan to become preg-
nant, suggest effective contraception (expert consensus).
2. Many pregnancies are unplanned, and substance use in the
first few weeks of pregnancy can have repercussions (LE)
and be a source of stress for women (expert consensus).
Provide information about the dangers of substance use
early in pregnancy (expert consensus).
3. Recommend that men quit drinking alcohol 3–6 months
before conception (expert consensus).
Provide information about the risk of PS to the woman’s
own health and possible interactions with contraception (ex-
pert consensus):
1. If she has more than 7 alcoholic drinks per week: warn
about the increased risk of breast cancer;
2. if she smokes cannabis, discuss estrogen plus progestin
contraception (based on recommendations for tobacco
and pregnancy);
3. if her use of PS is excessive, the risk of loss of self-control
that can result in forgetting to use the pill or condom
and the consequent risk of unexpected pregnancy make it
preferable to prescribe long-acting contraception;
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Professional’s approach
Immediate approach
-See patient again within 10–15 days
Monitoring of pregnancy**
-Pregnancy should be considered a high-risk pregnancy: the opinion
of an obstetrician-gynecologist and/or other specialist should be
requested to discuss if there is an indication for close medical
monitoring (risk of miscarriage, fetal death in utero, gestational
hypertension) and additional ultrasound follow-up.
-Suggest early prenatal care with a midwife or a doctor trained in
addiction care to assess the overall situation, offer support adapted
to the patient’s problems and resources, and set up brief
interventions or motivational support.
Management of substance use
-Suggest a physical, laboratory, addiction, and psychiatric evaluation
by a specialized addiction team.
Support
-Set up regular, coordinated multidisciplinary follow-up during
pregnancy and in the year after birth.
Actions to take at delivery
-A neonatal examination should be performed by a professional
trained in FASD and withdrawal syndrome.
Breastfeeding
-Breastfeeding should be encouraged, but only after neonatal
reassessment of substance use. A woman who is breastfeeding
should be informed of the benefits of quitting for the child and
should be supported in this process.
4. patients who use opioids should be warned about the dan-
ger to the fetus of withdrawal during pregnancy and the
possibility of replacement therapies compatible with preg-
nancy and breastfeeding.
Appointments during pregnancy
Address the issue of PS use when pregnancy is confirmed,
during the early prenatal interview, and at each pregnancy
follow-up appointment. It is important to ask the question not
only at the first appointment. The woman may only report us-
ing PS after several appointments, once a relationship of trust
has been established. Gestational hypertension should prompt
questions about substance use.
Also address this issue at each ultrasound and routinely
at the detection of a growth disorder, placental vascular ab-
normality, or fetal malformation, as well as late in pregnancy,
especially if the woman expresses the desire for anonymous
childbirth (that is, to surrender the child for adoption), and
during the prebirth anesthesia appointment.
Evaluate exposure to alcohol, cannabis, cocaine, and med-
ications by asking pregnant women about their use in the
S29

weeks and months preceding this pregnancy: this less imme-
diately guilt-inducing approach makes it possible to evaluate
the risk early in pregnancy.
To respect women’s needs,203 focus the discourse on preg-
nancy. Ask her how she found out she is pregnant. When?
Note the date. Calculate the term. Ask about the medical, sur-
gical, and obstetric history, up to this appointment. Then in-
quire about stressors, living conditions, PS use, etc. Knowing
as much as possible about the patient’s lifestyle, resources, and
needs will facilitate offering her suggestions for appropriate
support. It is helpful to ask patients for their consent: “Now
I need to ask you some personal questions to better monitor
your pregnancy (to take better care of your child). Do I have
your permission?” If tobacco, alcohol, drugs, or PS medications
are used, include them among the medical risk factors for the
pregnancy (see box 1).
During regular prenatal care (pregnancy monitoring), any
PS use by a pregnant woman should be considered misuse.
Advise her to quit, but not alcohol or opiates, because a semi-
urgent referral to an addiction professional is required for de-
pendence on alcohol (as withdrawal must be medically super-
vised) and opiates (withdrawal is contraindicated and opioid
replacement therapy is indicated). Make the connection with
motherhood: obtain her consent to disclose information to
the maternity team and set up a meeting with the pediatric
team before childbirth to prepare the parents for specific care
of the child.
Box 1. Referring women having PS use
If PS use constitutes a risk for the pregnancy (slight
to high level of risk), seek the advice of an obstetrician-
gynecologist to adapt the pregnancy monitoring methods
(expert consensus).
If PS use constitutes a risk for the fetus or infant (mod-
erate or high level), seek the advice of a pediatrician re-
garding care of the child at birth and to schedule follow-up
(expert consensus).
If PS use is problematic for the health of the woman
or her unborn child, offer a referral to an addiction care
professional (expert consensus).
During childbirth
If substance use is excessive, it is advisable to remain vigilant
to:
• the risk of delayed diagnosis of the onset of labor due to im-
paired perception of urgency and postponed decision mak-
ing
• interpretation of the fetal heart rate, which is less responsive
in cases of opioid dependence
• administration of ORT during labor at the usual times to
avoid withdrawal syndrome and
• pain assessment. Regular, heavy PS use often results in a
lower threshold of pain.
Local and regional anesthesia is possible regardless of the
substance used, as long as there is no medical contraindication
(expert consensus). As a reminder, nalbuphine (NUBAIN) is
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contraindicated in patients taking methadone or buprenor-
phine. See 2009 French Society of Anesthesia and Resuscita-
tion (SFAR) recommendation.202
The prescription of analgesics must take current and/or
history of opioid dependence into account (expert consen-
sus).
Receiving the newborn and making skin-to-skin contact
will be identical to conventional situations, with the same
rules of vigilance.
Postpartum follow-up
Certain clinical signs should suggest possible PS use and cause
professionals to question the mother after childbirth. These
include especially maternal heart problems, signs of with-
drawal in mother and/or child, neonatal growth restriction,
and dysmorphism syndrome or malformations that may sug-
gest FAS. Some PS use would require specific neonatal care
(Box 2).
Box 2. Neonatal care in the context of PS use
If ORT, alcohol, cocaine, or amphetamines are used
near the time of birth:
- It is advisable to monitor the newborn for floppy infant
syndrome and/or withdrawal (expert consensus).
- Prioritize parent-child closeness and nondrug meth-
ods: reduction of stimuli, holding, skin-to-skin contact,
swaddle bathing, swaddling, etc. (expert consensus).
If there is a risk of opioid withdrawal syndrome, the new-
born should be monitored by a pediatric team and assessed,
preferably along with the mother, by using the Finnegan or
Leipzig score. Its expression may be atypical when more than
one substance is involved. Treatment depends on the child’s
cravings. It begins with nursing care to minimize nonsensory
or environmental stimulation, maintain an optimal tempera-
ture, react quickly to signals from the infant, and achieve opti-
mal caloric intake. When necessary, this care is supplemented
by the use of morphine hydrochloride.125
In the event of treatment with methadone or buprenor-
phine, maternal pain perception is increased in the postpar-
tum period, particularly for 24 to 48 hours after a cesarean
birth, which may make adjunct analgesics necessary.
The approach to the possibility of breastfeeding should
be holistic: Is taking the substance compatible with adequate
mothering for the child? What is the risk/benefit balance?
What risk reduction approach should be taken to this sub-
stance use (see Box 3)?
Box 3. PS use and breastfeeding
- Alcohol: Advise against breastfeeding in the event of on-
going regular consumption. In the event of occasional
consumption of an alcoholic beverage, it is advisable to
wait at least 2 hours before breastfeeding (expert con-
sensus).
Volume 67, No. S1, November/December 2022

- Cannabis: Advise against breastfeeding in the event of
ongoing use (expert consensus).
- Heroin, cocaine, and amphetamines: Contraindicate
breastfeeding (expert consensus).
- Methadone or buprenorphine: Recommend breastfeed-
ing (expert consensus).
In the event of occasional cocaine use by a breastfeeding
woman, recommend that she express and discard the milk for
24–48 hours.138
Discharge instructions
Setting up a postnatal follow-up network that is medical as
well as psychological and social — attending physician, child
protection services, addiction specialist, psychiatrist — and
provides ongoing addiction care of the mother is imperative
for coordinated action.
The couple should be reminded of the increased risk
of SUID when using PS, particularly with regard to co-
sleeping/bed sharing (expert consensus).
In case of accidental ingestion by the child, warn par-
ents of the risk of serious cannabis poisoning and the risk
of overdose with methadone (expert consensus).
A child at risk of FASD should receive early and prolonged
developmental follow-up modeled on that of vulnerable in-
fants (expert consensus). Prevention of postpartum depres-
sion, which can increase the risk of relapse, is a priority (expert
consensus).
ACKNOWLEDGMENTS
The authors thank the coordinators (Chloé Barasinski,
Clermont-Ferrand; Rémi Béranger, Rennes; Catherine Salin-
ier, Gradignan; Cécile Zaros, Paris) and the other work-
ing group experts (Julie Bercherie, Paris; Jonathan Bernard,
Paris; Nathalie Boisseau, Clermont-Ferrand; Aurore Camier,
Paris; Romain Dugravier, Paris; Anne Evrard, Lyon; Anne-
Sophie Ficheux, Brest; Ronan Garlantézec, Rennes; Manik
Kadawathagedara, Rennes; Anne Laurent-Vannier, Saint-
Maurice; Marion Lecorguillé, Paris; Cécile Marie, Clermont-
Ferrand; Françoise Molénat, Montpellier; Fabienne Pelé,
Rennes; Brune Pommeret de Villepin, Lille; Mélie Rousseau,
Loos; Virginie Rigourd, Paris; Laurent Storme, Lille; Stéphanie
Weiss, Chambéry)who contributed to the discussions, as well
as to the production and validation of this text. The authors
also thank the members of the reading group who proofread
all the texts (see short document for complete list204 ).
CONFLICT OF INTEREST
This article was originally published online in French and has
been translated for publication in the Journal of Midwifery
& Women’s Health. The publication of this article has been
funded by the Collège National des Sages-Femmes de France
(French National College of Midwives).
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Appendix

Impact of psychoactive substance use on fertility

Products Data References Level of evidence

cannabis Men: Diminution LH and testosterone, oligospermia Nassan Fl 2019 LE4 Longitudinal study
and reduction of spermatozoid mobility
Women: reduced ovulation due to diminution of Warner T. 2014 LE4 Literature review
FSH-LH-strogen and increased prolactin Fronczak 2012
cocaine Men and women: Diminished fertility Fronczak 2012 LE4 Literature review
But recruitment bias (history of sexually transmitted Samplasti 2014 LE 2 Prospective cohort
infections, multiple use with tobacco and cannabis) study
Men: Erectile dysfunction (hyperprolactinemia)
amphetamines Men: Diminished fertility but no studies without Fronczak 2012 LE4 Literature review
associations with other products
opioids/ORT Men: Diminished fertility but no studies without Fronczak 2012 LE4 Literature review
associations with other products
Men and women: Inhibition of the hypothalamic
pituitary axis and hyperprolactinemia

Journal of Midwifery & Women’s Health r www.jmwh.org S37