DR.

LISELOTTE POCHARD (Orcid ID : 0000-0002-9271-5278)

Accepted Article
PROF. JOELLE MICALLEF (Orcid ID : 0000-0002-7172-7835)

DR. MARYSE LAPEYRE-MESTRE (Orcid ID : 0000-0002-5494-5873)

Article type : Original Article

Impact of pregnancy on psychoactive substance use among women with substance use

disorders recruited in addiction specialized care centers in France

Running title: Psychoactive substance use and pregnancy

Liselotte POCHARD a, c,*, Julie DUPOUY b, Elisabeth FRAUGER c, d, Adeline GIOCANTI c,

Joëlle MICALLEF c, d, Maryse LAPEYRE-MESTRE a, b, French Addictovigilance Network.

a
Centre d’Evaluation et d’Information sur la Pharmacodépendance-Addictovigilance de
Toulouse, Service de Pharmacologie clinique, CHU de Toulouse, Faculté de médecine, 37
allées Jules Guesde, 31000 Toulouse
b
UMR Inserm 1027, Université Toulouse 3, Faculté de Médecine, 37 Allées Jules Guesde,
31073 Toulouse cedex, France
c
Centre d’Evaluation et d’Information sur la Pharmacodépendance Paca Corse, Service de
Pharmacologie Clinique et Pharmacovigilance, Hôpital de la Timone, 13005 Marseille
d
Aix-Marseille Université, Institut de Neurosciences de la Timone, UMR 7289 CNRS,
Campus Timone, 13005 Marseille, France

*Corresponding author
Dr Liselotte Pochard
CEIP-Addictovigilance PACA-Corse
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process, which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/fcp.12346
This article is protected by copyright. All rights reserved.
 Service de Pharmacologie clinique et Pharmacovigilance
Hôpital Timone, CHU Marseille, Bât. F
264, rue St Pierre, 13385 Marseille Cedex 5
Accepted Article
Phone : +334.91.38.80.18
Fax : +334.91.47.21.40
E-mail : liselotte.pochard@ap-hm.fr

This article is protected by copyright. All rights reserved.

 ABSTRACT

Pregnancy can be a motivation for decrease in drug abusing but may also represent a period of
Accepted Article
high vulnerability for relapse. We aimed to assess psychoactive substance use among women
with substance use disorders followed in addiction care centers in France.
We analyzed data from women aged 15-44 years included in the ‘Observation of illegal drugs
and misuse of psychotropic medication survey’ (OPPIDUM), an annual cross-sectional survey
collecting details on psychoactive substances used. Characteristics of women included in
2005 to 2012 yearly surveys were compared depending on their pregnant or not pregnant
status. Factors, including pregnancy, associated with illicit substance use and medication
misuse were investigated through logistic regression.
The study included 518 pregnant and 6345 non pregnant women. 85.3% pregnant women
were on Opioid Maintenance Therapy (vs 77.1% of non-pregnant). Pregnancy was associated
with lower illicit substance use (adjusted OR 0.71 [0.58-0.88]) and with lower medication
misuse (0.66 [0.49-0.89]), whereas financial insecurity and living as a couple were associated
with increased risk. Raising children was significantly associated with less risk of substance
use. Each substance taken separately, the part of women using illicit substance or misusing
medication did not differ depending on whether they were pregnant or not, except for heroin
(24.5% in pregnant vs 17.9% non-pregnant ; <0.001).
This nationwide study provides new insights into psychoactive substance use in a large mixed
population of women with drug use disorders. Results outline the challenge of preventing
drug use and initiating care strategies with a specific approach on socio-economic
environment.

Keywords: Women, pregnancy, substance use disorders

This article is protected by copyright. All rights reserved.

Accepted Article
INTRODUCTION

Psychoactive substance use seems to affect more and more women. Most psychoactive
substances cross the placenta and may affect fetal development and cause neo-natal
complications: spontaneous abortion, fetal distress, intrauterine growth retardation, small birth
weight, pre-term delivery, neo-natal abstinence syndrome [1]. Furthermore, the lifestyle often
associated with psychoactive substance abuse (poor financial or social conditions,
malnutrition, poor obstetric care, injecting practices, infectious diseases, violence and alcohol
use) may contribute to deleterious effects on the unborn child and on his long-term
development [2]. Given these risks, pregnancy can be a motivation for discontinuation or
decrease in drug abusing and an opportunity to initiate a drug dependence treatment.
Population-based studies have shown a lower prevalence of psychoactive substance use
during pregnancy [3], suggesting behavioral changes toward reduction in consumption. Most
of these studies do not include women with substance use disorders, and focus only on
tobacco, alcohol or cannabis.
Studies conducted in maternity units among opioid-dependent or drug user show that pregnant
women tend to decrease their drug consumption although they did not manage to remain
drug-free throughout pregnancy (even under opiate maintenance treatment (OMT)) [4]. Most
of these studies assessed the fetal effect of drug intake or the effectiveness of different
treatment approaches on pregnancy outcome and thus did not provide data about patterns of
psychoactive drug use in this specific population. Finally, some studies tried to measure
abstinence rate among pregnant-women with a product based-approach and retrospective
collection of consumption data before pregnancy [5].
OPPIDUM (for Observation of illegal drugs and misuse of psychotropic medication) is a
nationwide survey that collects information on abuse and dependence in patients attending
care in addiction care centers in France [6-9]. We aimed to assess risk factors associated with
psychoactive substance abuse by comparing patterns of substance use according to the
presence of ongoing pregnancy in women of childbearing age with substance use disorders.
Factors, including pregnancy, associated with illicit substance use and medication misuse
were investigated through logistic regression.

This article is protected by copyright. All rights reserved.

 METHODS
Accepted Article
Data were derived from the OPPIDUM survey, a cross-sectional and multicenter survey
carried out every year over a 4-week period in October since 1995. It was developed by the
French Addictovigilance Network [10-12] in order to monitor changes in the consumption of
psychoactive substances used, and alert about the use of new products or new routes of
administration. Methods and results have already been published [6-9]. Briefly, on a voluntary
basis, centers include patients with psychoactive substance abuse or dependence criteria (as
defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) or
under Opioid Maintenance Therapy (OMT). Patients who use alcohol or tobacco exclusively
are not included. Socio-demographic information and data about all substances (either illicit
or medication) used during the 7 days before the interview were anonymously collected
through a standardized questionnaire. The current study focused on women of childbearing
age (15-44 years) who were included in the OPPIDUM survey during 8 data collection
periods from 2005 to 2012, whatever the type of centers: centers for care, support and
prevention (CSAPA), harm reduction centers (CAARUD), hospitals and prison units. The
design was not changed and no supplementary data were collected.

We used the following variables: i) Socio-demographic data: patient already known at the
center, age, current pregnancy, employment, family situation (living as a couple, raising
children), education, living in stable accommodation, and financial resources; ii) addictive
behavior elements (alcohol dependence, tobacco consumption, nature and age of first
substance use and first substance that had led to dependence (excepting tobacco and alcohol));
iii) current participation in a OMT program (methadone, buprenorphine or other opioid), and
center managing OMT program.

For each psychoactive substance, the following variables were used: frequency of intake,
route(s) of administration, concomitant alcohol use, means of acquisition, consumption as part
of an abuse or dependence and daily dosage for medication only.
According to the type of psychoactive substance consumed during the previous week, two
additional outcome variables ̶ illicit substance and medications ̶ were constructed: i) “illicit
substance use” was defined as having used any illicit substance and ii) “medication misuse”
was defined as having used medication non-medically. Medication misuse was defined by one
of the following patterns: route(s) of administration not recommended by the Summary of

This article is protected by copyright. All rights reserved.

 Product Characteristics, illegal acquisition, consumption as part of an abuse [as defined in
DSM-IV - Manuel diagnostique et statistique des troubles mentaux (Diagnostic and Statistical
Manual of Mental Disorders)]. Due to a lack of medical data, we used a proxy for “psychiatric
Accepted Article
comorbidities under treatment”, such as the consumption of at least one psychotropic
medication (antidepressant, antipsychotic, mood stabilizer, and sedative/hypnotic drug) in the
context of therapeutic use (not meeting medication misuse criteria mentioned above).

The analysis compared pregnant and non-pregnant women. We performed two models (one
for each outcome) of multivariate logistic regression to investigate factors (including
pregnancy) associated with “illicit substance use” and “medication misuse”. The analysis was
stratified by year of survey to remove possible variations over time, and all eligible variables
associated with the outcomes in the univariate analysis (p<0.20) were included in the
multivariate models. Backward elimination procedure was used to obtain the final models.
After checking, no interaction terms were included in the models. Results are presented as
adjusted odds ratios, with their 95% confidence interval (CI). The significance level was set at
p<0.05. All analyses were performed using SAS version 9.2 software.

This was an observational study performed on strictly anonymous data, routinely collected by
clinical staff, and which therefore did not require any ethics committee approval, in line with
the French regulations for mandatory reporting of addiction cases by health professionals.

RESULTS

During the period 2005-2012, 6,863 women were of childbearing age (i.e. 88.1% of all
women) and 518 (7.5%) were pregnant at the time of the survey. Table 1 presents socio-
demographic and behavior characteristics of pregnant and non-pregnant women. Pregnant
women were younger, more often living as a couple, unemployed and less educated than non-
pregnant. They were more likely to be raising children than non-pregnant.

Table 1

Illicit substance use and medication misuse

Table 2 presents illicit substance use and medication misuse in the previous week according to
pregnancy. Illicit substance use was less frequently reported in pregnant than in non-pregnant
women, except for heroin use. Pregnant women misused medication less frequently than non-

This article is protected by copyright. All rights reserved.

 pregnant. Overall, 51.2% pregnant women and 59.2% non-pregnant reported using at least
one illicit substance and/or misused medication (p= 0.0004), and 14.0% of pregnant women
and 10.1% of non-pregnant were both illicit and medication users (p=0.014).The mean
Accepted Article
number of illicit substances used was higher in pregnant women than in non-pregnant (1.51 ±
0.83 vs 1.33 ± 0.64 ; p<10-4), whereas the mean number of misused medication was not (1.23
± 0.66 vs 1.28 ±0.66 ; p>0.05). Injection practice was not different among pregnant and non-
pregnant (table 1) as well as rate of substances consumed every day (about 70% for
medications misused and 43% for illicit substance used, falling to about 12% after excluding
cannabis). There was no significant difference between pregnant and non-pregnant women
concerning misuse criteria distribution.
Table 2
Concerning consumption patterns, 7.9% of pregnant women had injected at least one
psychoactive substance vs 8.6% (p>0.05) (table 1). Among pregnant women misusing
prescription drugs, 77.1% (vs 71.4% in non-pregnant) had illegally obtained at least one of
those, 36.1% (vs 43.9%) had used non-recommended administration route and 26.2% (vs
30.9%) reported abusive use. Non-medically used prescription drugs were mostly prescribed
by a practitioner but to a less extent in the pregnant group (50.0% vs 60.3%), with the most
important part bought on black market or given by someone (44.9% vs 31.8%).

Treatment of opioid dependence

As seen in table 3, pregnant women were more likely to be treated than non-pregnant women.
Methadone tended to have been initiated more recently in pregnant women (39.1% had started
methadone program in the weeks or months prior to the survey vs 34.5%; p=0.087). The OMT
program was more often monitored by a different care setting when the women were
pregnant, primarily by general practitioners for buprenorphine. Among women on OMT
program, 24% of the pregnant women had used heroin compared to 16.2% of non-pregnant
participants (p<10-4). On the other hand, pregnant women were not more likely to have
misused their OMT than non-pregnant ones.
Table 3

Psychiatric comorbidities under treatment

Psychiatric comorbidities concerned 13.9% of pregnant and 27.1% of non-pregnant women

(p<10-4). Drugs used were benzodiazepines (73.6% of pregnant and 66.6% of non-pregnant

This article is protected by copyright. All rights reserved.

 women), antidepressants (38% in both groups), antipsychotics (18% vs 25%) and mood-
stabilizers (6.4% vs 1.4%) (not significant).
Accepted Article
Multivariate logistic regression

Table 4 presents the results of the multivariate regression models and factors associated with
illicit substance use and medication misuse among all reproductive-aged women. Pregnancy
was significantly associated with less illicit substance use (adjusted OR: 0.71 [0.58-0.88]) as
well as with less medication misuse (adjusted OR: 0.66 [0.49-0.89]). Old age was protective
for illicit substance use and at risk for medication misuse, i.e. reduces with increasing age for
illicit substance use, and at the same time increases with increasing age for medication
misuse. Financial insecurity was associated with both illicit substance use and medication
misuse, and raising children was significantly associated with less risk for both. For illicit
substance use, risk was positively associated with living as a couple/with a partner.
Medication misuse risk was higher among women who did not live in stable accommodation.
Concomitant alcohol use was positively associated with both illicit substance use and
medication misuse and, for illicit substance use only, the risk increased with the duration of
dependence.
Treated psychiatric comorbidities were associated with less use and misuse, and beneficial
effect of OMT depended on both substance of abuse and OMT itself. For instance, women on
buprenorphine were more at risk of medication misuse.
Table 4

DISCUSSION

In a large sample size of pregnant women and women of childbearing age with substance use
disorders, we observed a lower risk of illicit substance use and medication misuse associated
with pregnancy, however this study highlights the difficulty of remaining drug-free for
dependent women despite pregnancy and emphasizes the seriousness of this public health
issue. Indeed, in our population, prevalence of substance abuse in pregnant women did not
differ so much from non-pregnant and many of them presented some dangerous consumption
patterns.

This article is protected by copyright. All rights reserved.

 Yet, after adjusting for relevant covariates, pregnancy remained associated with lower relative
risk of substance misuse with a 1.5-fold decrease for both illicit and medication. Additionally,
we highlighted other factors associated with substance use and misuse among both pregnant
Accepted Article
and non-pregnant women. Typically, inclusion in the OMT program was correlated with less
psychoactive substance use and misuse, except for buprenorphine which increased the risk of
medication misuse.
A treated psychiatric disorder appeared to be a protective factor against substance use and
misuse. Patients treated with psychotropic medication without misuse (so probably well-
stabilized) were more likely to adhere to OMT program and care. It is particularly challenging
to diagnose these comorbidities and to treat them especially during pregnancy, because of the
reluctance to expose pregnant women to psychotropic drugs [13]. The risk of illicit substance
use decreased with age, which may result from a high rate of cannabis use in the young
population. Conversely and in accordance with the literature [14], age was positively
correlated with medication misuse. Living as a couple was at risk of illicit substance use only
(and not of medication misuse), which outlines the negative influence of social environment
(factors, such as family and friends, were not explored here). Tuten et al reported earlier
treatment discontinuation among women with drug-using partners than among those with
drug-free partners [15]. In another study, Fischer et al described, in women with opioid
dependence, an important rate of addicted partner, and more successful treatment when the
partner was also on treatment [16]. Interestingly, the independent protective effect of the
presence of child or children to raise suggests a long-term impact on substance use even after
delivery. Actually, women already raising children could be considered as being less
frequently abusing drugs; but high-rate drug abusers could have lost their parenting rights.

This multicenter study provides new insights into psychoactive substance use in a large mixed
population of women with substance use disorders, all over France. Unlike most other studies
on women and pregnant women, the OPPIDUM survey explores more fully substance misuse
patterns apprehending use purpose, route of administration and means of acquisition in real
life practice.
However, our study presents methodological limitations. First, consumption data relied on
self-report questionnaire only, exposing to potential under-reporting bias, especially among
pregnant women. Nevertheless, as all these women were recruited in specialized centers, we
can assume that the under-reporting rate was lower and acceptable, since there are no legal
considerations regarding drug use during pregnancy in France. Although psychoactive

This article is protected by copyright. All rights reserved.

 substance use during pregnancy is often reported to the children welfare services, it does not
necessarily lead to the removal of the child. Second, the study is not representative of all
pregnant women with substance use disorders because of their high vulnerability and their
Accepted Article
low participation in voluntary care. We can assume that most pregnant women seen in these
centers were not yet included in obstetric care. Finally, even though the survey covered 68
French areas, the voluntary basis of center care recruitment could affect the representativeness
of the population.

In addition, some data which can influence substance abuse remained unknown (gestational
age, pregnancy planning, prenatal care, nature of management of addictive disease). For
example, gestational age was not reported while studies show a decrease in substance use
throughout pregnancy [3, 4, 17]. Moreover, a planned pregnancy could strongly promote early
management of substance use disorders. Additionally, we had neither information on prenatal
care nor on the nature of addictive disease management, although comprehensive integrated
and compassionate care models are more effective on consumption decrease in particular [18].
Finally, as it was a cross-sectional survey, we could not know at what point pregnancy
happened in the history of the addictive disease. Some had been able to plan a pregnancy as a
result of the benefit gained by the introduction of treatment (both on physical, mental and
socio-economic state), or being surprised by a newfound fertility through the establishment of
a substitution protocol [19]. Others had been forced to reduce their consumption because of
occurrence of medical and obstetrical complications involving the well-being/welfare of the
unborn child. Ideally, the women’s consumption should be evaluated before and throughout
pregnancy.

Although pregnant women were less likely to have used illicit substances, those who
continued despite pregnancy seemed to use as much or more than non-pregnant, especially for
heroin. As well, unsafe consumption patterns (such as injectable route) were not less common.
While following an OMT treatment, 24% of pregnant women reported heroin and 11.5%
cocaine use. It is more than the rate observed in two French studies conducted in maternity
units, i.e. 16% and 9% for Lejeune et al [4] and, 15.6% and 6.9% for Lacroix et al [20].
This may be related to the most part of pregnant women at risk of drug abuse (younger, poor
socio-economic condition), and a rate of pregnant women initiating methadone a little more
recently, directly because of pregnancy. According to Lejeune et al, up to 70% of pregnant

This article is protected by copyright. All rights reserved.

 dependent women were not provided with substitution therapy before pregnancy [4] and
studies have shown a high rate of unintended pregnancy among this population [21].
On the contrary, psychotropic medication drug misuse like benzodiazepine, common in this
Accepted Article
population [22] was infrequent. It might be related to our own definition of medication misuse
criteria, which is far more restrictive than illicit substance use, not considering high daily dose
intake for example. Moreover, frontier between ‘abuse’ and ‘dependence’ as purpose of drug
use could be difficult to define by participants. Nevertheless, this can reflect the apprehension
to treat women when they are pregnant and therefore a limited access during pregnancy.
Alcohol consumption was even less likely to affect pregnant women than non-pregnant. These
results are in line with Moore et al [23] who described more frequent stop or decrease in
alcohol and amphetamine intake than tobacco and cannabis at the time of pregnancy among
drug-using women. The current state of knowledge identifies alcohol as the only psychoactive
substance with proven teratogenic effect [24] whereas other drugs are not without risk. Fetal
exposure to benzodiazepine has been suspected to result in an increase in risk of oral cleft and
major malformation [25]; even though this risk remains to date uncertain [26, 27], MDMA
intake (3,4-méthylène-dioxy-methamphétamine) was suspected to have caused cardiac
malformation after exposition in utero [28]. Thus, sympathomimetic effect of cocaine can lead
to fetal and maternal hypertension with risk of placental abruption [29] and preterm delivery
[30]. While it is difficult to determine individual effects, cannabis smoking, which concerned
almost one third of the included pregnant women, can lead to low birth weight and
prematurity [31]. On the other hand, opioid withdrawal in pregnancy is associated also with
increased risks of fetal distress, abortion and preterm birth [32]. Note that the composition of
illicit drugs may be different from expected [33].
Finally, discontinuation or reduction in substance use also depends on knowledge and
perception of the risks associated with substance use. In 1999, Murphy and Rosenbaum [34]
interviewed women with substance use about their perception of potential harm of drug to the
fetus; those who consumed heroin considered it as safe, and those who consumed some
psychostimulants did not know about the risks. Another study highlighted reluctance of
discontinuation not just because of physical and mental pain of abstinence but also because of
prejudice on social relationship [35].

Pregnancy could represent a window of opportunity to initiate treatment and reduce drug
abuse. To confirm our results, a prospective study should be performed on a large cohort of
women included before they become pregnant.

This article is protected by copyright. All rights reserved.

 ACKNOWLEDGEMENTS
We wish to thank all the centers that participated in the OPPIDUM surveys. These annual
surveys are carried out with the support of the French Medicine Drug Agency (Agence
Accepted Article
Nationale de Sécurité du Médicament et des produits de santé, ANSM).
With regards to the present work, ANSM had no role in the design, analysis, and
interpretation of the data; or in the preparation, review, or approval of the manuscript.

This article is protected by copyright. All rights reserved.

 REFERENCES
1. Kuczkowski K.M. The effects of drug abuse on pregnancy. Curr. Opin. Obstet.
Gynecol. (2007) 19 578–585.
Accepted Article
2. Bauer C.R., Shankaran S., Bada H.S. et al. The Maternal Lifestyle Study: drug
exposure during pregnancy and short-term maternal outcomes. Am. J. Obstet.
Gynecol. (2002) 186 487–495.
3. Ebrahim S.H., Gfroerer J. Pregnancy-Related Substance Use in the United States
During 1996-1998. Obstet. Gynecol. (2003) 101 374–379.
4. Lejeune C., Simmat-Durand L., Gourarier L. et al. Prospective multicenter
observational study of 260 infants born to 259 opiate-dependent mothers on
methadone or high-dose buprenophine substitution. Drug. Alcohol depend. (2006) 82
250–257.
5. Forray A., Merry B., Lin H. et al. Perinatal substance use: a prospective evaluation of
abstinence. Drug. Alcohol Depend. (2015) 150 147–155.
6. Frauger E., Moracchini C., Le Boisselier R. et al. OPPIDUM surveillance program: 20
years of information on drug abuse in France. Fundam. Clin. Pharmacol. (2013) 27
672–682.
7. Frauger E., Nordmann S., Orleans V. et al. Which psychoactive prescription drugs are
illegally obtained and through which ways of acquisition? About OPPIDUM survey.
Fundam. Clin. Pharmacol. (2012) 26 549-556.
8. Nordmann S., Frauger E., Pauly V. et al. Misuse of buprenorphine maintenance
treatment since introduction of its generic forms: OPPIDUM survey.
Pharmacoepidemiol. Drug. Saf. (2012) 21 184-190.
9. Daveluy A., Frauger E., Peyrière H. et al. Which psychoactive substances are used by
patients seen in the healthcare system in French overseas territories? Results of the
OPPIDUM survey. Fundam. Clin. Pharmacol. (2017) 31 126-131.

10. Jouanjus E., Gibaja V., Kahn J.P. et al. Therapie. Signal identification in
addictovigilance: the functioning of the French system. Therapie. (2015) 70 113-131.
11. Peyriere H., Nogue E., Eiden C. et al. Evidence of slow-release morphine sulfate
abuse and diversion: epidemiological approaches in a French administrative area.
Fundam. Clin. Pharmacol. (2016) 30 466-475.

12. Daveluy A., Géniaux H., Eiden C. et al. Illicit drugs or medicines taken by
parachuting. Fundam. Clin. Pharmacol. (2016) 30 185-190

This article is protected by copyright. All rights reserved.

 13. Greenfield S.F., Back S.E., Lawson K. et al. Substance abuse in women. Psychiatr.
Clin. North. Am. (2010) 33 339–355.
14. Simoni-Wastila L., Strickler G. Risk Factors Associated With Problem Use of
Accepted Article
Prescription Drugs. Am. J. Public. Health. (2004) 94 266–268.
15. Tuten M., Jones H.E. A partner's drug-using status impacts women's drug treatment
outcome. Drug. Alcohol Depend. (2003) 70 327–330.
16. Fischer G. Treatment of opioid dependence in pregnant women. Addiction (2000) 95
1141–1144.
17. Havens J.R., Simmons L.A., Shannon L.M. et al. Factors associated with substance
use during pregnancy: results from a national sample. Drug Alcohol Depend. (2009)
99 89–95.
18. Jones H.E., Haug N., Silverman K. et al. The effectiveness of incentives in enhancing
treatment attendance and drug abstinence in methadone-maintained pregnant women.
Drug. Alcohol Depend. (2001) 61 297–306.
19. Bell J., Harvey-Dodds L. Pregnancy and injecting drug use. Brit. Med. J. (2008) 336
1303–1305.
20. Lacroix I., Berrebi A., Garipuy D. et al. Buprenorphine versus methadone in pregnant
opioid-dependent women: a prospective multicenter study. Eur. J. Clin. Pharmacol.
(2011) 67 1053–1059.
21. Heil S.H., Jones H.E., Arria A. et al. Unintended pregnancy in opioid-abusing
women. J. Subst. Abuse Treat. (2011) 40 199–202.
22. Jones J.D., Mogali S., Comer S.D. Polydrug abuse: a review of opioid and
benzodiazepine combination use. Drug. Alcohol depend. (2012) 125 8–18.
23. Moore D.G., Turner J.D., Parrott A.C. et al. During pregnancy, recreational drug-using
women stop taking ecstasy (3,4-methylenedioxy-N-methylamphetamine) and reduce
alcohol consumption, but continue to smoke tobacco and cannabis: initial findings
from the Development and Infancy Study. J. Psychopharmacol. (2010) 24 1403–1410.
24. Sokol R.J., Miller S.I., Reed G. Alcohol abuse during pregnancy: an epidemiologic
study. Alcohol Clin. Exp. Res. (1980) 4 135–145.
25. Dolovich L.R., Addis A., Vaillancourt J.M. et al.Benzodiazepine use in pregnancy and
major malformations or oral cleft: meta-analysis of cohort and case-control studies.
Brit. Med. J. (1998) 317 839–843.
26. Okun M.L., Ebert R., Saini B. A review of sleep-promoting medications used in
pregnancy. Am. J. Obstet. Gynecol. (2015) 212 428–411.

This article is protected by copyright. All rights reserved.

 27. Hurault-Delarue C., Damase-Michel C., Finotto L. et al. Psychomotor developmental
effects of prenatal exposure to psychotropic drugs: a study in EFEMERIS database.
Fundam. Clin. Pharmacol. (2016) 30 476-482.
Accepted Article
28. McElhatton P.R., Bateman D.N., Evans C. et al. Congenital anomalies after prenatal
ecstasy exposure. The Lancet. (1999) 354 1441–1442.
29. Addis A., Moretti M.E., Ahmed Syed F. et al. Fetal effects of cocaine: an updated
meta-analysis. Reprod. Toxicol. (2001) 15 341–369.
30. Gouin K., Murphy K., Shah P.S. Knowledge Synthesis group on Determinants of Low
Birth Weight and Preterm Births. Effects of cocaine use during pregnancy on low
birthweight and preterm birth: systematic review and metaanalyses. Am. J. Obstet.
Gynecol. (2011) 204 340.e1–e12.
31. Hayatbakhsh M.R., Flenady V.J., Gibbons K.S. et al. Birth outcomes associated with
cannabis use before and during pregnancy. Pediatr. Res. (2012) 71 215–219.
32. Luty J., Nikolaou V., Bearn J. Is opiate detoxification unsafe in pregnancy? J Subst.
Abuse Treat. (2003) 24 363–367.
33. Daveluy A., Miremont-Salamé G., Rahis A.C. et al. Medicine or ecstasy? The
importance of the logo. Fundam. Clin. Pharmacol. (2010) 24 233-237.
34. Murphy S. and Rosenbaum M. Pregnant women and drugs. Combating stereotype and
stigma. New Brunswick: Rutgers University Press. 2009.
35. Leppo A. « Subutex is safe »: Perceptions of risk in using illicit drug during
pregnancy. Int. J. Drug Policy. (2012) 23 365–373.

This article is protected by copyright. All rights reserved.

 Table 1 : Socio-demographic characteristics and addictive behaviors of 15-44 years old pregnant and
non-pregnant women included in the OPPIDUM survey during the 2005 to 2012 data collection
Non pregnant
Pregnant women p-
women
Accepted Article
(N=518) value
(N=6345)
Mean age (± sd) (years) 28.53 ± 5.93 30.23 ± 7.20 < 10¯4
N % N %
Employment
Yes 150 29 2291 36.1 < 10¯4
No 352 68 4003 63.1
Unknown 16 3.1 51 0.8
Living as a couple
Yes 352 68 2582 40.7 < 10¯4
No 161 31 3650 57.5
Unknown 5 1 113 1.8
Raising children
Yes 264 51 2160 34 < 10¯4
No 247 47.7 4062 64
Unknown 7 1.4 123 1.9
Resources
Severe financial insecurity 29 5.6 456 7.2 0.411
Financial insecuritywith social income 231 44.6 2648 41.7
Regular income 237 45.8 2993 47.2
Unknown 21 4.1 248 3.9
Stable accommodation
Yes 429 82.8 5151 81.2 0.420
No 75 14.5 955 15.1
Unknown 14 2.7 239 3.8
Education
> 8 years of school 440 85 5673 89.4 0.005
< 8 years of school 52 10 473 7.5
Unknown 26 5 199 3.1
Care center
CAARUDa 7 1.4 170 2.7 < 10¯4
CSAPAb 373 72 5705 89.9
Hospital setting 133 25.7 297 4.7
Prison unit 5 1 173 2.7
First contact with the center
Yes 128 24.7 1211 19.1 0.004
No 386 74.5 5038 79.4
Unknown 4 0.8 96 1.5
Tobacco
Non user 61 11.8 498 7.9 < 10¯4
5-10 cigarettes/d 136 26.3 1137 17.9
10-20 cigarettes/d 164 31.7 2787 43.9
>20 cigarettes/d 152 29.3 1854 29.2
Unknown 5 1 69 1.1

This article is protected by copyright. All rights reserved.

 Alcohol dependence
Yes 55 10.6 958 15.1 0.002
No 455 87.8 5345 84.2
Accepted Article
Unknown 8 1.5 42 0.7
Concomitant alcohol use with psychoactive drugs
Yes 71 13.7 1283 20.2 0.002
No 440 84.9 4975 78.4
Unknown 7 1.4 87 1.4
Route of administration in the previous weekc
Injection 41 7.9 545 8.6 0.655
Intranasal route 129 24.9 1274 20.1 0.010
Inhalation 173 33.4 2431 38.3 0.030
Fist substance leading to dependence
Heroin 386 74.5 4172 65.8
Cannabis 58 11.2 934 14.7
Cocaïne (including crack) 21 4.1 292 4.6
Amphetamines 2 0.4 82 1.3
Other substance not prescribed 0 0 15 0.2
Benzodiazepine 8 1.5 127 2
Opioid analgesic 10 1.9 173 2.7
OMTd 10 1.9 108 1.7
Other medication 2 0.4 86 1.4
Unknown 21 4.1 356 5.6
Mean (± sd) duration of dependence (years) 9.22 (± 5.71) 10.65 (± 6.79) < 10¯4
a
Centres d'Accueil et d'Accompagnement à la Réduction des risques pour Usagers de Drogues (Harm
reduction centers)
b
Centre de Soins, d’Accompagnement et de Prévention en Addictologie (Centers for care, support and
prevention)
c
At least one psychoactive substance
d
Opiate Maintenance Treatment

This article is protected by copyright. All rights reserved.

 Table 2 : Illicit substance use and medication misuse in the prior week in pregnant and non-pregnant
women
Accepted Article
Pregnant women Non pregnant
(N=518) women (N=6345) p-
value
N % N %
Illicit substance (≥ 1 substance used) 241 46.5 3284 51.8 0.025
Cannabis 166 32 2202 34.7 0.240
Cocaine (and crack) 57 11 801 12.6 0.316
<0.00
Heroine (and illicit opiates) 127 24.5 1133 17.9
1
Amphetamine 10 1.9 147 2.3 0.680
Hallucinogen (synthetic or natural) 3 0.6 69 1.1 0.386
Poppers and solvents 0 0 5 0.1 1.000
Medication (≥ 1 substance misused) 61 11.8 1113 17.5 0.001
Benzodiazepine 28 5.4 391 6.2 0.551
Methadone 13 2.5 224 3.5 0.272
Buprenorphine 24 4.6 415 6.5 0.107
Strong opioid analgesics 5 1.4 112 1.8 0.240
Weak opioid analgesics 2 0.4 34 0.5 1.000
Ketamine 1 0.2 24 0.4 1.000
Psychostimulant 1 0.2 7 0.1 0.466
Antidepressant 0 0 19 0.3 0.394
Neuroleptic 1 0.2 25 0.4 0.718
Other sedative or hypnotic drug 0 0 30 0.5 0.166
Description of medication misuse criteria
Route(s) of administration not
22 36.1 489 43.9 0.283
recommended
Illegal acquisition 47 77.1 795 71.4 0.422
Consumption as part of an abuse 16 26.2 344 30.9 0.529

This article is protected by copyright. All rights reserved.

 Table 3 : Description of opiate maintenance treatment among pregnant and non-pregnant women in
childbearing age of OPPIDUM survey between 2005 and 2012
Pregnant women Non pregnant p
(n=518) women (n=6345) valu
Accepted Article
n % n % e
<
Opiate substitution treatment 442 85.3 4889 77.1
10¯4
Methadone 312 70.6 3278 67.1 0.32
Buprenorphinea 127 28.7 1571* 32.1
Other opioidb 3 0.68 40 0.82
Methadone n=312 n=3278
57.3 ± 31.1 [2- 58.0 ± 31.9 [1- 0.70
Daily dosage (mean ± SD [min-max]) (n)
200] (293) 420] (3106) 5
Treatment onset
0.08
Few weeks or few months 122 39.1 1131 34.5
7
>1 years 162 51.9 1910 58.3
Unknown 28 9 237 7.2
Program’s responsibility
<
Survey care center 230 73.7 2849 86.9
10¯4
General practitioner 45 14.4 143 4.4
Other center 31 9.9 177 5.4
Unknown 6 1.9 109 3.3
<0.0
Heroin use in the prior week 79 25.3 570 17.4
01
0.56
Methadone misusec 9 2.9 121 3.7
9
Buprenorphine n=127 n=1571
6.9 ± 4.3 [0.4-16] 7.9 ± 6.2 [0.2-90] 0.09
Daily dosage (mean ± SD [min-max]) (n)
(121) (1433) 1
Treatment onset
0.18
Few weeks or few months 26 20.5 440 28.0
6
>1 years 88 69.3 989 63
Unknown 13 10.2 142 9
Program’s responsibility
0.01
Survey care center 65 51.2 1004 63.9
3
General practitioner 49 38.6 409 26
Other center 8 6.3 76 4.8
Unknown 5 3.9 82 5.2
0.78
Heroin use in the prior week 16 21.3 218 13.9
9
0.25
Buprenorphine misusec 21 16.5 333 21.2
8
a
including 15 patients on Suboxone® (buprenorphine + naloxone) in 2012
b
morphine sulfate, codeine, dihydrocodeine, fentanyl, analgesic buprenorphine
c
in accordance with medication misuse criteria

This article is protected by copyright. All rights reserved.

 Table 4 : Logistic regression models exploring factors associated with illicit substance use and
medication misuse among all reproductive aged women included in OPPIDUM survey between 2005
and 2012
Illicit substance use Medication misuse
p-
p- Adjuste
Accepted Article
Adjuste 95% CI 95% CI valu
value d OR
d OR e
0.58- 0.49- 0.00
Pregnancy 0.71 0.88 0.001 0.66 0.89 6
Age (reference : 15-19 years)
0.39- <0.00 0.10
20-24 0.55 0.76 1 1.33 0.95-1.86 2
0.28- 0.03
25-29 0.39 0.54 <10-4 1.45 1.03-2.03 2
0.22- 0.00
30-34 0.31 0.43 <10-4 1.66 1.18-2.36 4
0.18- 0.00
35-39 0.25 0.36 <10-4 1.66 1.16-2.38 6
0.10- 0.73
40-44 0.15 0.21 <10-4 1.07 0.73-1.56 7
Resources (reference : regular income)
1.11- <0.00 <10-
4
Financial insecurity 1.24 1.39 1 1.84 1.59-2.13
0.85- 0.09
Unknown 1.14 1.54 0.378 1.36 0.95-1.95 5
0.74- <10-
4
Raising children 0.83 0.94 0.002 0.67 0.57-0.79
0.53- 0.92
Unknown 0.87 1.42 0.577 1.02 0.65-1.61 6
1.03-
Living as a couple 1.15 1.28 0.016 - - -
0.53-
Unknown 0.89 1.51 0.665 - - -
0.00
Stable accommodation - - - 0.75 0.63-0.89 1
0.48
Unknown - - - 1.14 0.79-1.63 9
0.48- <10-
Treated psychiatric comorbidities 0.55 0.62 <10-4 0.58 0.49-0.68 4

Smoking tobacco (reference : non-

smoking)
1.76- 0.19
≤ 20 cigarettes/d 2.16 2.66 <10-4 1.20 0.91-1.60 5
1.78- 0.00
>20 cigarettes/d 2.22 2.76 <10-4 1.69 1.26-2.26 1
1.44- 0.81
Unknown 2.43 4.12 0.001 0.91 0.43-1.92 0
1.42- <10-
Associated alcohol use 1.64 1.88 <10-4 1.91 1.64-2.23 4

0.13- 0.01
Unknown 0.22 0.38 <10-4 0.32 0.13-0.80 5
Dependence duration (reference : < 10
years)
≥ 10 years 1.28 1.11- 0.001 - - -

This article is protected by copyright. All rights reserved.

 1.48
0.61-
Unknown 0.78 0.98 0.036 - - -
Maintenance program (reference :
Accepted Article
methadone)
3.98- <10-
-4 4
No program 4.68 5.50 <10 1.76 1.48-2.11
0.55- <10-
-4 4
Buprenorphine 0.62 0.71 <10 2.61 2.23-3.06
0.29- 2.69- <10-
4
Other opioid 0.57 1.14 0.112 5.21 10.10
Care center (reference : CSAPAa)
1.48- <10-
b -4 4
CAARUD 2.16 3.15 <10 3.09 2.22-4.29
1.33- 0.30
Hospital 1.68 2.13 <10-4 1.16 0.88-1.52 6
1.30- <10-
4
Prison 1.88 2.71 0.001 2.56 1.84-3.57
-
Variables not retained in the final model after univariate analysis
a
Centre de Soins, d’Accompagnement et de Prévention en Addictologie
b
Centres d'Accueil et d'Accompagnement à la Réduction des risques pour Usagers de Drogues

This article is protected by copyright. All rights reserved.