Maintenance agonist treatments for opiate-dependent pregnant women.
Author(s): Minozzi S(1), Amato L, Bellisario C, Ferri M, Davoli M.
Affiliation(s): Author information:
(1)Department of Epidemiology, Lazio Regional Health Service, Via di Santa Costanza,
53, Rome, Italy, 00198.
Publication date & source: 2013, Cochrane Database Syst Rev. , 12:CD006318
BACKGROUND: The prevalence of opiate use among pregnant women can range from 1%
to 2% to as high as 21%. Heroin crosses the placenta and pregnant,
opiate-dependent women experience a six-fold increase in maternal obstetric
complications such as low birth weight, toxaemia, third trimester bleeding,
malpresentation, puerperal morbidity, fetal distress and meconium aspiration.
Neonatal complications include narcotic withdrawal, postnatal growth deficiency,
microcephaly, neuro-behavioural problems, increased neonatal mortality and a
74-fold increase in sudden infant death syndrome.
OBJECTIVES: To assess the effectiveness of any maintenance treatment alone or in
combination with psychosocial intervention compared to no intervention, other
pharmacological intervention or psychosocial interventions for child health
status, neonatal mortality, retaining pregnant women in treatment and reducing
the use of substances.
SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Trials Register
(September 2013), PubMed (1966 to September 2013), CINAHL (1982 to September
2013), reference lists of relevant papers, sources of ongoing trials, conference
proceedings and national focal points for drug research. We contacted authors of
included studies and experts in the field.
SELECTION CRITERIA: Randomised controlled trials assessing the efficacy of any
maintenance pharmacological treatment for opiate-dependent pregnant women.
DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures
expected by The Cochrane Collaboration.
MAIN RESULTS: We found four trials with 271 pregnant women. Three compared
methadone with buprenorphine and one methadone with oral slow-release morphine.
Three out of four studies had adequate allocation concealment and were
double-blind. The major flaw in the included studies was attrition bias: three
out of four had a high drop-out rate (30% to 40%) and this was unbalanced between
groups.Methadone versus buprenorphine: the drop-out rate from treatment was lower
in the methadone group (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.41
to 1.01, three studies, 223 participants). There was no statistically significant
difference in the use of primary substance between methadone and buprenorphine
(RR 1.81, 95% CI 0.70 to 4.69, two studies, 151 participants). For both, we
judged the quality of evidence as low. Birth weight was higher in the
buprenorphine group in the two trials that could be pooled (mean difference (MD)
-365.45 g (95% CI -673.84 to -57.07), two studies, 150 participants). The third
study reported that there was no statistically significant difference. For APGAR
score neither of the studies which compared methadone with buprenorphine found a
significant difference. For both, we judged the quality of evidence as low. Many
measures were used in the studies to assess neonatal abstinence syndrome. The
number of newborns treated for neonatal abstinence syndrome, which is the most
critical outcome, did not differ significantly between groups. We judged the
quality of evidence as very low.Methadone versus slow-release morphine: there was
no drop-out in either treatment group. Oral slow-release morphine seemed superior
to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI
1.00 to 5.77, one study, 48 participants). We judged the quality of evidence as
moderate.Only one study which compared methadone with buprenorphine reported side
effects. For the mother there was no statistically significant difference; for
the newborns in the buprenorphine group there were significantly fewer serious
side effects.In the comparison between methadone and slow-release morphine no
side effects were reported for the mother, whereas one child in the methadone
group had central apnoea and one child in the morphine group had obstructive
apnoea.
AUTHORS' CONCLUSIONS: We did not find sufficient significant differences between
methadone and buprenorphine or slow-release morphineto allow us to conclude that
one treatment is superior to another for all relevant outcomes. While methadone
seems superior in terms of retaining patients in treatment, buprenorphine seems
to lead to less severe neonatal abstinence syndrome. Additionally, even though a
multi-centre, international trial with 175 pregnant women has recently been
completed and its results published and included in this review, the body of
evidence is still too small to draw firm conclusions about the equivalence of the
treatments compared. There is still a need for randomised controlled trials of
adequate sample size comparing different maintenance treatments.
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