Transcript Nicotine and pregnancy

Nicotine Use in Pregnant Women
and its Effect on Offspring
Jessica Kozlowski, Pak Kei Chan
Alan Lu, Shunzhi Chang
2014 Nov 25
PHM142 Fall 2014
Coordinator: Dr. Jeffrey Henderson
Instructor: Dr. David Hampson
1. Introduction
 Negative
effects of smoking on mother and fetus:
 Neurobehavioral
effects
 Cardiovascular effects
 Reduced infant birth weight
 Premature delivery
 Infant death
1. Introduction
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15-25% of mothers smoking during pregnancy
Majority of women who quit for pregnancy start again
after their child’s birth
45% of fathers smoking at the time of their child’s birth
Why not quit? Start smoking cessation?
- nicotine addiction
Nicotine replacement therapy (NRT) better alternative
for the fetus.
Is it safe?
Minimal human data about effect of direct nicotine
exposure in pregnant women, but a lot about tobacco
smoke exposure.
2. Pharmacokinetics of Nicotine
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Clear liquid b.p.247 °C
Small molecule
Mw = 162
Miscible in water
logP = 1.2, amphiphilic
Fast absorption
Cross Blood-brain barrier (10~20s)
and placenta barrier
2. Pharmacokinetics of Nicotine
3. Cigarette Smoking during Pregnancy
- Effects on offspring
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Few studies to accurately evaluate effects in
pregnant women using nicotine replacement
therapy (NRT). Most effects studied in rodents.
Short term effects: low birth weight and sudden
infant death syndrome.
Long-term effects:
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Neurobehavioral problems.
Hypertension.
Obesity and type 2 diabetes.
Respiratory dysfunction.
Childhood cancers (leukemia/lymphoma).
Impaired fertility.
3. Cigarette Smoking during Pregnancy
- Neurobehavioural problems
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Attention-deficit hyperactivity disorder, learning
disabilities, behavioral problems, increased anxiety.
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In rats, nicotine is a
neuroteratogen,
which compromises
development of
critical neural
pathways.
10 uM
100 uM
3. Cigarette Smoking during Pregnancy
- Hypertension
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Associated with in utero exposure to cigarette
smoking.
Perinatal nicotine
In rats, perinatal nicotine
exposure
exposure:
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Enhances AT1 and attenuates
AT2 gene expression.
Increases Ca2+ sensitivity of
myofilaments leading to
vasoconstriction and
development of hypertensive
phenotype in adulthood.
AT1: Angiotensin II receptor type 1.
AT2: Angiotensin II receptor type 2.
AT1/AT2 ratio ↑
↑ Ca2+ sensitivity of
myofilaments
↑ Vasoconstriction
Hypertension
4. Methods of Smoking Cessation
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Bupropion (Zyban)
Nicotine Replacement Therapy
Other (Hypnosis, acupuncture, quitting
gradually, quitting “Cold Turkey”)
4. Preventative Methods
- Bupropion
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Initially prescribed to treat various forms of
depression.
It was discovered that smoking cravings and
withdrawal effects were reduced.
Inhibition of neurotransmitter uptake
Study conducted showed no increased risk of
congenital malformation in fetal development.
Summary Slide
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Nicotine can readily cross the blood-brain barrier and the placental
barrier.
It is also an ingredient found in tobacco and it’s primary responsible
for sustaining addictive effects.
Smoking during pregnancy has been shown to cause
neurobehavioral and cardiovascular abnormalities.
Nicotine acts as a neuroteratogen and induce neurobehavioral
problems which include: Attention deficit hyperactivity disorder
(ADHD), learning disabilities, or increased risk of nicotine addiction.
An example of a cardiovascular problem is hypertension.
Studies conducted in rats have shown that perinatal nicotine
exposure :
- Alters the gene expression of AT1 and AT2
- Myofilaments are more sensitive to Ca2+
- Vasoconstriction occurs easily, thus causing hypertension
The bottom line:
Absentia > Bupropion > NRT > cigarette smoking, with the best
alternative to smoking being quitting prior to pregnancy.
Thank You
Very Much!
References
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