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

ate and lesser, concomitant effects on foetal
heart rate but larger effects are caused by
smoking cigarettes (14), (15). It has been
suggested that nicotine-induced vasoconstriction
might affect placental blood
flow and could be responsible for smokingrelated
reduced foetal growth in utero.
Nicotine is also a neurotoxin and long term
nicotine exposure to pregnant rats is
associated with adverse changes in infant
rats’ behavioural and cognitive responses
(14), (15).
Safety:neurotoxicity
■ Smoking in pregnancy =
infants’ behavioural problems (ADHD)
- Hypothesis, observational
■ Experimental animal studies
- High dose maternal nicotine infusion =
infant rat behavioural problems
■ No experimental human studies
It has been hypothesised, therefore, that
nicotine may be the constituent of smoking
which causes the behavioural and cognitive
problems observed in infants born to
maternal smokers (4-16). However, some
experts believe that the doses of nicotine
used in these rodent studies were much
higher than was necessary to compare with
the nicotine doses generated by humans use
of NRT and consequently, these studies are
of little relevance to use of NRT in pregnancy
(17). There are currently no experimental
studies investigating the impact of maternal
nicotine exposure in pregnancy or in
subsequent infant cognition behaviour,
however.
Human studies
Currently, there are only 4 humans studies
providing data on the safety of nicotine in
pregnancy. A Danish placebo RCT
randomised 250 women to nicotine or
placebo patches and found that infants born
to women in the group who received
nicotine were heavier than those in the
placebo group (18). The mean difference in
birth weight was small (186g [95% CI 35 to
336g]) and, hence, is not of clinical
significance, but is of theoretical interest
because it does not support the hypothesis
that nicotine is the substance in tobacco
smoke responsible for of foetal growth
restriction. Another RCT randomised 181
women to cognitive behavioural therapy
alone or with added NRT, but this trial was
stopped early due to a non-significant
doubling of adverse events in the NRT arm
(19). Adverse events included some
premature births at 35-37 weeks gestation
which are of minimal clinical significance.
The final analysis of trial data suggested that
the higher rate of early birth in the nicotine
arm occurred because, by chance, the rate of
previous pre-term birth was higher in
P.V. Pataka.
39 Recommendations during pregnancy - Tim Coleman
(17) Hussein J, Farkas S,
MacKinnon Y, Ariano RE,
Sitar DS, Hasan SU.
Nicotine doseconcentration
relationship and
pregnancy outcomes in
rat: Biologic plausibility
and implications for
future research.
Toxicology & Applied
Pharmacology 2007;
218(1): 01.
(18) Wisborg K,
Henriksen TB, Jespersen
LB, Secher NJ. Nicotine
patches for pregnant
smokers: a randomized
controlled study.
Obstetrics & Gynecology
2000; 96(6): 967-971.
(19) Pollak KI, Oncken
CA, Lipkus IM, Lyna P,
Swamy GK, Pletsch PK et
al. Nicotine replacement
and behavioral therapy
for smoking cessation in
pregnancy. American
Journal of Preventive
Medicine 2007; 33(4):
297-305.
(20) Morales-Suarez-
Varela MM, Bille C,
Christensen K, Olsen J.
Smoking habits, nicotine
use, and congenital
malformations.
Obstetrics & Gynecology
2006; 107(1): 51-57.
(21) Tata LJ, Hubbard RB,
Lewis SA, Smith CJP,
Coleman TJ. Maternal
smoking, use of nicotine
replacement therapy in
pregnancy and
congenital
malformations in
offspring: A case-control
study nested within a
pregnancy cohort.
Unpublished work,
submitted for
publication.
(22) Dempsey D, Jacob P,
III, Benowitz NL.
Accelerated metabolism
of nicotine and cotinine
in pregnant smokers.
Journal of Pharmacology
& Experimental
Therapeutics 2002;
301(2): 594-598.