Available online at www.sciencedirect.com
Drug and Alcohol Dependence 96 (2008) 69–78
Buprenorphine and methadone treatment of opiate dependence
during pregnancy: Comparison of fetal growth and neonatal
outcomes in two consecutive case series
, Markus Heilig
, Ihsan Sarman
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
Laboratory of Clinical and Translational Studies, NIAAA/NIH, Bethesda, MD, USA
Department of Clinical Science, Karolinska Institute, Southern Hospital Stockholm, Sweden
Received 16 August 2007; received in revised form 27 January 2008; accepted 28 January 2008
Available online 19 March 2008
Aim: To compare the effects of fetal buprenorphine and methadone exposure during maintenance treatment of pregnant heroin dependent subjects.
Design and setting: A population based comparison of consecutive, prospectively followed buprenorphine-exposed pregnancies in Stockholm
County, Sweden, to retrospectively analyzed consecutive methadone-exposed pregnancies.
Participants: All 47 pregnancies in 39 women with opiate dependence and buprenorphinemaintenance treatment 2001–2006, and all 35 methadone-
exposed pregnancies (26 women) 1982–2006 in Stockholm County.
Measurements: Intrauterine growth, birth outcome, malformations, neonatal adaptation, withdrawal syndrome and infant mortality.
Findings: Buprenorphine-exposed pregnancies resulted in 47 uneventful live births (2 twin pairs), 1 stillbirth (for which no explanation was
found) and 1 miscarriage. The birth weight of the infants was normal. Neonatal abstinence syndrome (NAS) occurred in 19 cases (40.4%), the
majority mild in nature and only 7 (14.9%) needing withdrawal treatment. Compared to 35 infants born after intrauterine methadone exposure at
the same hospital since 1982 (77.8% of them exhibiting NAS and 52.8% needing withdrawal treatment), there were signiﬁcant advantages with
buprenorphine treatment: birth weight was higher, due to longer gestation. Incidence of NAS of any intensity, as well as incidence of NAS that
required pharmacological treatment was lower, while length of hospital stay was shorter. When buprenorphine treatment started pre-conception,
NAS at any level was signiﬁcantly less frequent than in subjects with post-conception initiated treatment (7/27, 26%; 12/20, 60%, respectively).
Conclusions: Data from this non-randomized comparison suggest that buprenorphine may offer advantages for treatment of opiate dependence
© 2008 Elsevier Ireland Ltd. All rights reserved.
Keywords: Pregnancy; Heroin; Maintenance treatment; Methadone; Buprenorphine; Neonatal abstinence; Fetal development
Similar to other countries where heroin problems are preva-
lent, about one fourth of Sweden’s estimated 10,000 heroin
dependent subjects are women, most of whom are of childbear-
ing age (Guttormsson, 2005). Use of contraceptives is sporadic
in this population. This is partly because of the lifestyle asso-
ciated with illicit drug use, but also because chronic opiate use
Corresponding author at: Stockholm Southern Hospital, Department of Pae-
diatrics, Sachsska Children’s Hospital, S-118 83 Stockholm, Sweden.
Fax: +46 8 616 4194.
E-mail address: firstname.lastname@example.org (I. Sarman).
commonly disrupts the menstrual cycle, resulting in a percep-
tion that contraceptive measures are not needed (Bai et al., 1974;
Genazzani et al., 1993; Harlow et al., 2003). When pregnan-
cies ultimately occur in these subjects, the fetus is exposed to
the drugs taken by the mother, since psychoactive drugs are
highly lipophilic, and therefore easily pass the blood–brain and
the placenta barrier alike.
Heroin dependence in pregnant women has been managed in
various ways in different treatment settings (for an overview,
see Kaltenbach et al., 1998). Involuntary residential care, as
well as diverse behavioral and pharmacological treatments have
all been used, individually or in combination. Systematic eval-
uation is scant. Treatment efforts typically need to address a
wide range of physical, mental and social problems. Outside of
0376-8716/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.