Nicotine replacement therapy … - Carlos A ... - Entretiens du Carla

(23) Kapur B, Hackman
R, Selby P, Klein J, Koren
G. Randomized, doubleblind,
placebo-controlled
trial of nicotine
replacement therapy in
pregnancy. Current
Therapeutic Research,
Clinical & Experimental
2001; 62(4): 274-278.
(24) Hegaard HK,
Kjaergaard H, Moller LF,
Wachmann H, Ottesen B.
Multimodal intervention
raises smoking cessation
rate during pregnancy.
Acta Obstetricia et
Gynecologica
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813-819.
(25) Pollak K, Oncken
CA, Lipkus I, Lyna P,
Swamy G, Pletsch P et al.
Effectiveness of Adding
Nicotine Replacement to
Cognitive Behavioral
Therapy for Smoking
Cessation in Pregnant
Smokers: The Baby
Steps Trial. American
Journal of Preventive
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305.
(26) Coleman T,
Thornton J, Britton J,
Lewis S, Watts K,
Coughtrie MW et al.
Protocol for the
smoking, nicotine and
pregnancy (SNAP) trial:
double-blind, placeborandomised,
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replacement therapy in
pregnancy. 1186. BMC
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2007; 7:2.
women randomised to group. The nonblinded
trial design could also have resulted
in biased reporting of adverse events
amongst the NRT group and although birth
weight was monitored, no significant
differences between trial arms were noted.
Two observational epidemiological studies
have investigated the relationship between
NRT use in pregnancy and congenital
abnormalities. One analysed data from
almost 77,000 pregnancies within a Danish
birth cohort, finding an association between
reported nicotine use in the first trimester of
pregnancy and subsequent foetal
malformation (OR 1.61; 95% CI 1.01 – 2.58)
(20). A second case control study, however,
analysed data from almost 51,000 live births
and compared pregnant women who had
received prescriptions for NRT with those
who did not but found no association
between receiving NRT on prescription and
foetal abnormality (OR 1.56; 95% CI 0.85 –
2.86) (21). In both studies findings could have
arisen because of unmeasured (and
therefore non-adjusted for) factors causing
confounding and further evidence is
required.
In summary, there is no compelling
evidence that medicinal nicotine use in
pregnancy is safer or more harmful than
smoking and more research is required. The
current expert consensus that using NRT is
probably safer in pregnancy than smoking is
predominantly based on theoretical
considerations (10).
Nicotine in pregnancy:
effectiveness for smoking
cessation
Although NRT is of unquestionable
effectiveness when used outside of
pregnancy, pregnant women metabolise
nicotine and cotinine 60% and 140% faster
respectively than non-pregnant smokers
(22).
This means that standard does of nicotine
replacement therapy may not generate
sufficient plasma levels of nicotine in
pregnant women to effectively substitute for
the nicotine that they would have received
by smoking: higher doses may be need in
pregnancy for NRT to be effective.
This could explain why the three trials
meta analysed in the Cochrane review of
smoking cessation interventions in
pregnancy provide no evidence for the
effectiveness of NRT when used for smoking
cessation in pregnancy (9-18-23-24). The
open-label RCT which was stopped due to
increased adverse events, and which is not
included in the review analysis, did, however,
produce positive findings (25). This trial had
two primary outcomes: seven day point
prevalence smoking cessation at both 7 and
38 weeks of pregnancy. At 7 weeks, 7 day
point prevalence cessation was significantly
higher in the NRT arm (24% vs. 8%) and at
38 weeks, cessation in the NRT group was
still greater (18% vs. 7%), but no longer
statistically significant at ‘p’ value selected at
the outset of the study (p=0.025 – to allow
for two primary outcomes).
There are currently three ongoing studies
which should produce further information of
the safety and effectiveness of NRT in
pregnancy. These include two placebo RCTs;
one is based in Nottingham, England (26) has
currently recruited 50% of its target and the
second based in Paris, France and has
recently started recruiting. A third openlabel
RCT is based in the US and results are
due soon.
Consequently, in the next 5 years there
may be sufficient evidence to make more
definitive statements about the effectiveness
of NRT for smoking cessation in pregnancy,
but currently there is no evidence other than
theoretical, to suppose that it works.
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